Hangata ho pepesa methamphetamine le boitšoaro bo bobe ba thobalano ho ntlafatsa moputso oa lithethefatsi o latelang le ho baka boitšoaro bo bobe ba ho kopanela liphate ka likhoto tsa banna (2011)

J Neurosci. 2011 Nov 9;31(45):16473-82. doi: 10.1523/JNEUROSCI.4013-11.2011.

Frohmader KS, Lehman MN, Laviolette SR, Coolen LM.

mohloli o moholo

Lefapha la Anatomy le Cell Biology, Sekolo sa Bongaka sa Schulich le Phekolo ea meno, Univesithi ea Western Ontario, London, Ontario N6A5C1, Canada.

inahaneloang

Basebelisi ba Methamphetamine (Meth) ba tlaleha ho eketsa thabo ea thobalano, balekane ba bangata ba thobalano le ho kopanela liphate ntle ho ts'ireletso ka lebaka la tahlehelo ea taolo ea thibelo. Boitšoaro bona bo qobelloang ka thobalano bo thusa ho ata ha tšoaetso ea thobalano, empa motheo oa neural oa sena ha o tsejoe. Pele re ne re theha paradigm ea boitšoaro bo qobelloang ba thobalano ho litoeba tsa banna moo lefu la visceral le hlahisoang ke lithium chloride le neng le entsoe ka boitšoaro ba thobalano (Davis et al., 2010; Frohmader et al., 2010a). Boithuto ba hajoale bo ile ba hlahloba litlamorao tsa taolo e pheta-phetoang ea Meth mabapi le ts'ebetso ea thobalano, boitšoaro bo qobelloang ba thobalano, le moputso oa thobalano kapa Meth. Taba ea pele, liphetho li bonts'itse hore litsamaiso tse supileng tsa letsatsi le letsatsi tsa 2 mg / kg, empa eseng 1 mg / kg, Meth e ile ea eketsa latency ho qala ho tlolelana. Ho senyeha hona ho ile ha totobala 30 min kamora taolo ea ho qetela ea Meth, empa e qhalane ka mor'a 1 kapa 7 d ea ho tlohela lithethefatsi ka mor'a moo. Ho pepesetsoa khafetsa 1 mg / kg Meth ho hlahisitse boitšoaro bo qobelloang ba ho batla thobalano libeke tsa 2 kamora ho tsamaisoa ha Meth ea ho qetela. Phello ena e ne e its'etleha holima taolo ea Meth ka nako e ts'oanang le boiphihlelo ba thobalano 'me e ne e sa bonoe ho liphoofolo tse nang le tsebo ea thobalano tse amohelang Meth feela. Ntle le moo, Meth e tšoanang le boiphihlelo ba botona le botšehali bo ntlafalitseng boikhethelo ba sebaka (CPP) bakeng sa Meth, le Methane e tšoanang le ho hola ho bapisoa le Meth kapa mating feela. Ka lehlakoreng le leng, CPP bakeng sa mating e le 'ngoe e ne e fokotsehile. Ka bobeli, tlhaiso-leseling ena e bonts'a hore setsoalle lipakeng tsa ts'ebeliso ea lithethefatsi le mating li ka hlokoa bakeng sa ho bontša boitšoaro bo qobelloang ho tsa thobalano mme bo amana le moputso o eketsehileng o batlang ponelopele ea nako e tšoanang ea Meth.

Karolo e fetilengKarolo e latelang

Selelekela

Maloetse a amanang le bophelo bo botle ba thobalano ka har'a batho ba lemalloang a hlahisitse tlhokomeliso ka litlamorao tsa lithethefatsi tsa tlhekefetso ho tsa thobalano, kaha tšebeliso e mpe ea lithethefatsi e amanang le ts'ebetso ea thobalano e sa bolokehang e bakang ho ata ha tšoaetso ea thobalano, ho kenyelletsa le vaerase ea immunodeficiency virus (HIV) (Crowe le George, 1989; Peugh le Belenko, 2001; Sánchez et al., 2002; Raj et al., 2007; Fisher et al., 2011). Litlamorao tsena tsa lithethefatsi mabapi le boitšoaro ba thobalano li ngotsoe hantle bakeng sa psychostimulant methamphetamine (Meth). Basebelisi ba Meth hangata ba tlaleha takatso e matla ea thobalano, thabo le thabo mme ba supa lintlha tsena e le tšusumetso ea mantlha ea tšebeliso ea lithethefatsi (Semple et al., 2002; Schilder et al., 2005; Green le Halkitis, 2006). Ntle le moo, tlhekefetso ea Meth e tloaetse ho amahanngoa le tahlehelo ea taolo ea boitšoaro bo bobe ba thobalano kapa boitšoaro bo tlamang ba ho etsa thobalano (Halkitis et al., 2001; McKirnan et al., 2001; Rawson et al., 2002; Green le Halkitis, 2006) le ho ata ha tšoaetso ea HIV (Frosch et al., 1996; Halkitis et al., 2001; Parsons le Halkitis, 2002).

Litlaleho tsa batho tse bonts'ang tšebeliso ea Meth e le ponelopele ea boits'oaro bo bobe ba thobalano e ipapisitse le litlaleho tsa boithati tse tsoang ho basebelisi ba Meth ba sa foleng tekanyo e tšepahalang bakeng sa kamano pakeng tsa ts'ebeliso ea Meth le boitšoaro ba thobalano (Frohmader et al., 2010b). Ka hona, lipatlisiso mabapi le liphetoho tse susumetsoang ke Meth tse amanang le boitšoaro ba thobalano tlasa liteko tsa taolo tse laoloang li sebelisa sebopeho sa phoofolo li hlokahala ho utloisisa kamano e rarahaneng pakeng tsa Meth le boitšoaro ba thobalano.

Haufinyane tjena, laboratori ea rona e ile ea hlahloba litlamorao tsa Meth e matla ea ho batla thobalano ho likhoto tsa banna (Frohmader et al., 2010a). Lithuto tsena li sebelisitse paradigm ea boemo bo botle ba ho kopanela liphate eo ho eona likhoto tsa banna li ithutileng ho amahanya mating le bokuli bo latelang ba visceral (Peters, 1983; Agmo, 2002). Hang ha kamano ena lipakeng tsa ho tlolelana le matla a ho hlasimolla e thehiloe, liphoofolo li ke ke tsa qala boitšoaro ba mating (Davis et al., 2010; Frohmader et al., 2010a). Metso ea ho itšupa nako ea libeke tse le 'ngoe tsa ente pele ho boemo e sitisitse ho fumana likarabo tse thibetsoeng tsa thobalano (Frohmader et al., 2010a). Kahoo, litoeba tse tona tsa Meth tse iketsisang li ne li batla boitšoaro ba thobalano le leha e le hore ho ts'oaroa ho ne ho amana le tšusumetso e mpe; hona ho ne ho thoe ke ho holofala kapa ho qobella.

Ha lithuto tse fetileng li hlahloba litlamorao tsa ente e mpe ea lithethefatsi le lipatlisiso tsa lipatlisiso tsa litla-morao tsa Methati mabapi le boitšoaro ba thobalano ba banna e haelloa, sepheo sa thuto ea morao-rao e ne e le ho etsa lipatlisiso ka litlamorao tsa taolo ea Meth ka likarolo tse fapaneng tsa boitšoaro ba thobalano. ts'ebetso, ho batla ka thobalano ka thobalano le moputso. Taba ea pele, litlamorao tsa phetisetso ea Meth ka ho ea mateng e ile ea lekoa kamora ts'ebetso ea lithethefatsi le kamora nako ea ho khaotsa ho sebelisa lithethefatsi ho khetholla liphetho tsa nakoana le tsa nako e telele tsa Meth mabapi le thobalano. Ka mor'a moo, ho ile ha hlahlojoa litlamorao tsa taolo e pheta-pheto ea Meth mabapi le boitšoaro bo bobe ba thobalano, ho kenya tšebetsong paradigm ea boemo bo tlase. Ntle le moo, ho ile ha khethoa hore na litloaelano tse ithutoang pakeng tsa ho pepesetsoa Meth le boits'oaro ba thobalano li bohlokoa bakeng sa litlamorao tsa Meth mabapi le boitšoaro bo bobe ba thobalano. Kamora nako, ho ile ha lekoa hore na ho pepesetsoa ha Meth ho hlahisa moputso o ntlafalitsoeng oa Meth le / kapa ho nyaloa, joalo ka ha ho khethollotsoe ke paradigms ea sebaka se ikhethileng (CPP).

Lisebelisoa le mekhoa

Lihlooho

Ho ile ha fumanoa likhoto tsa banna ba baholo ba Sprague Dawley (210-225 g) 'me tsa bolokoa ka ba babeli ba bong bo tšoanang ka mekotla e tloaelehileng ea Plexiglas (likhotla tsa lapeng) tse nang le lipeipi tsa PVC ea phaello ea tikoloho. Liphoofolo li ne li behiloe ka kamoreng e hlokometsoeng mochining oa 12 / 12 h o khutlisang lebone / lefifi (mabone a tima 11: 00 AM) ka lijo le metsi tse fumanehang. ad libitum. Liteko tsohle li entsoe nakong ea potoloho e lefifi tlasa khanya ea bofubelu. Li-femme tsa Stimulus (200-225 g; Charles River Laboratories) tse sebelisitsoeng bakeng sa boitšoaro ba thobalano li ile tsa lekanngoa ka bongata mme tsa amohela kenyelletso e kenellang e nang le 5% estradiol benzoate le 95% cholesterol. Ho susumetsa thobalano, batho ba batšehali ba ile ba fuoa 0.5 mg ea progesterone ho 0.1 ml ea oli ea sesame (sc) 4 h pele ho boitšoaro ba thobalano. Ts'ebetso ea liteko e amohetsoe ke Komiti ea Tlhokomelo ea Liphoofolo Univesithing ea Western Ontario le Komiti ea Univesithi ea Michigan ea Tlhokomelo ea Liphoofolo le Ts'ebeliso 'me e ne e lumellana le tataiso e boletsoeng ke Lekhotla la Canada mabapi le Tlhokomelo ea Liphoofolo le Likolo tsa Naha tsa Bophelo.

Moralo oa liteko

Boitšoaro ba thobalano

Teko ea hajoale e ile ea etsa lipatlisiso ka litlamorao tsa ho pheta-pheta hoa Methati mabapi le ts'ebetso ea thobalano le tšusumetso hang kamora ho ts'oaroa ha lithethefatsi le ho latela nako ea ho thibela lithethefatsi. Liroto tse mashome a mararo a metso e meraro tsa banna li fumane boiphihlelo ba thobalano litekong tse fapaneng tsa tlhahlobo (mating arenas; 60 × 45 × 50 cm) e nang le mealo e hloekileng ea ho robala nakong ea liketane tse hlano tsa beke le beke. Sebokeng ka seng, banna ba ne ba lumelloa ho nyalana le mosali ea amohelang molaetsa ho fihlela ho hlaha ponts'o e le 'ngoe kapa bakeng sa 1 h, ho sa etsahala letho pele. Bekeng e le 'ngoe ka mor'a seboka sa ho qetela sa ho tsofala, banna ba ile ba fuoa mokhoa oa liteko mme ba fuoa ente e sa sebetseng ea 1 ml / kg saline matsatsi a mararo a latellanang. Kamora ho entoa ka leng, liphoofolo li ile tsa beoa likamoreng tsa ts'ebetso ea Plexiglas locomotor (40.5 × 40.5 cm; Med Associates) e nang le li-arrow tsa 16 × 16 tsa photobeam; ts'ebetso ea locomotor e tlalehiloe bakeng sa 30 min. Ntle le ho rekota ts'ebetso ea ho ts'oara motho ka mora ente ea kalafo, ho beha ba batona likamoreng tsa polokelo ea tikoloho ho fane ka tikoloho e amanang le lithethefatsi e fapaneng le ea boitšoaro ba mating. Kamora moo, banna ba ile ba fumana ente ea letsatsi le letsatsi ea 1 kapa 2 mg / ml / kg Meth kapa koloi (saline, 1 ml / kg; n = 11 ka 'ngoe) bakeng sa matsatsi a 7 a latellanang. Kamora ho enteha ka ngoe, ba batona ba ne ba beoa kamoreng ea lits'ebeletso tsa locomotor mme tšebetso ea locomotor e tlalehiloe bakeng sa 30 min, ka mor'a moo ba khutlela mekotleng ea bona. Ka letsatsi la ho qetela la taolo ea Meth, banna ba ile ba tlosoa kamoreng ea tšebetso ea kamora kamore ea 30 mme ba beoa lebaleng la mating ho ea lekola litlamorao tsa Meth mabapi le boitšoaro ba thobalano. Liphoofolo li ile tsa lekoa hape bakeng sa boitšoaro ba thobalano litsing tsa ho ts'oaroa kamora 1 d kapa beke ea 1 ea ho tlohela lithethefatsi.

Nakong ea kemaro, ho ile ha bonoa le ho tlaleheloa litekanyetso tse tloaelehileng tsa boitšoaro ba thobalano, ho kenyelletsa le ho nyoloha (nako ho tloha ho kenyelletsong ea mosali ho ea pele) le ho kenella (nako ho tloha ho kenyelletsoa ha mosali ho ea ho pele), tse bonts'ang takatso ea thobalano (Hull et al., 2002), hammoho le latency ho ejaculation (nako ho tloha ho kenella pele ho isa ho emong), lipalo le ho kenella pele ho kemolo, le nako ea ho emisa, e le mehato ea ts'ebetso ea thobalano (Hull et al., 2002; Pfaus, 2009). Phapang lipakeng tsa lihlopha e ne e reriloe molemong o mong le o mong oa boits'oaro ba thobalano ho sebelisoa tlhahlobo ea Kruskal-Wallis eo e seng ea parametric le Dunn's post hoc papiso, maemong a bohlokoa a 0.05.

Ts'ebetso ea locomotor

Ketsahalo ea locomotor kamora ente e 'ngoe le e' ngoe ea Meth e ile ea hlahlojoa ho sebelisoa software ea tlhahlobo ea Med Associates ha sebaka se tsamauoa ka nako ea metsotso e 5. Ho se tšoane ha sehlopha ho ile ha hlahlojoa ho sebelisoa tlhahlobo ea Kruskal-Wallis eo e seng ea parametric le ea Dunn's post hoc papiso. Ho hlahloba methapo ea methapo ea methapo ea methapo ea methapo ea methapo ea methapo, tšebetso ea Meth nakong ea 10 ea ho qetela ea tlhahlobo e ne e bapisoa pakeng tsa letsatsi la pele le la bosupa la ente ka har'a sehlopha ka seng sa kalafo sa lithethefatsi se sebelisoang ka marang-rang. t liteko. Karolo ea bohlokoa ea 0.05 e sebelisitsoe ho lipapiso tsohle.

Boikutlo bo bobe ba ho qhekella thobalano

Leka 1.

Taba ea pele, likhoto tsa banna tsa 50 li ne li tloaetse ho kenngoa ka ente ea letsoai bakeng sa matsatsi a mararo a latellanang mme ba batona ba bile le boiphihlelo ba thobalano nakong ea likopano tse tharo. Pele ho karolo e 'ngoe le e' ngoe ea ho ikatisa, liphoofolo li ne li kenngoa ka 1 mg / kg Meth kapa 1 ml / kg saline (sc), e behiloeng ka arenas, mme, 30 min hamorao, ba ile ba lumelloa ho nyalana le mosali ea amohelang ho fihlela ejaculation kapa 1 h. Methati ea boitšoaro ba thobalano e ile ea tlalehoa mme ea hlahlojoa (bona Boitšoaro ba thobalano, kaholimo). Kamora libeke tse peli, liphoofolo li ile tsa fuoa mokhoa oa ho hloea thobalano le maemo a tlase. Tse tona li ile tsa aroloa ka lihlopha tse 'ne tsa liteko ho latela pretreatment (Meth kapa saline) le maemo [lithium chloride (LiCl) -paired kapa -unpaired]; lihlopha li ne li se na letsoai (n = 12), Meth-unpaired (n = 12), e nang le letsoai (n = 13), le Meth-paired (n = 13). Paradigm ea boemo bo botle e ne e kenyelletsa liteko tse robeli tse latellanang tsa 2 d. Ka letsatsi la pele, ba batona bohle ba ile ba beoa lebaleng la mating bakeng sa nako ea bolulo ea 10, kamora hore ho be le mosali ea amohelang. Tse tšehali li ne li fafatsoa ka ho hlapela oli ea almond molaleng le botlaaseng ba mohatla pele ho ho ts'oaroa, joalo ka ha ho bontšitsoe mekhoa ea boithuto e le ho tsamaisa mokhoa oa mokhoa oa banna le ho matlafatsa maemo (Lawrence le Kiefer, 1987; Agmo, 2002). Ba batona ba ne ba lumelloa ho nyalana le 30 min kapa ho fihlela ejaculation e le ngoe. Haeba ho kenella kahare ho ne ho sa etsahale kahare ho metsotso ea 15 ea pele, mating a ne a felisitsoe. Motsotso o le mong ka mor'a ho omisoa kapa ho emisoa ha liteko, banna ba ile ba fuoa ente ea 127.2 mg / kg ea intraperitoneal ea 10 ml / kg LiCl (banna ba paired) kapa saline (ba batona ba sa fepang). LiCl kapa saline li ne li fanoa ho sa tsotelehe hore na ho ruruha ho bile teng. Letsatsing le hlahlamang, ba batona ba sa sebetseng ba ile ba fumana ente ea 10 ml / kg ea LiCl ha ba batona ba paired ba fumana letsoai. Liphoofolo li ne li khutlisetsoa ka mokotleng oa lapeng ka mor'a ho entoa.

Leka 2.

Ho etsa liteko tsa litla-morao tsa Meth ka ho hloea thobalano le maemo a itseng ho ne ho ipapisitse le ho pepesetsoa nako e le 'ngoe ho Meth le ho nyaloa kapa ka lebaka la Meth feela, ho ile ha etsoa tlhahlobo e' ngoe. Malebela a bannan = 20) e fumane boiphihlelo ba thobalano nakong ea liketane tse hlano empa ntle le kalafo ea Meth kapa saline (n = 10 ka 'ngoe). Sebakeng seo, bekeng ea 1 kamora boiphihlelo ba thobalano, ba fumane liente tse supileng hang tsa letsatsi le letsatsi tsa Meth (1 mg / kg, sc) kapa saline le 2 libeke kamora moo ba ile ba beoa tlasa maemo a hlekefetsang a thobalano a amanang le thobalano (bona Teko ea 1, kaholimo).

Bakeng sa liteko ka bobeli le nakong ea teko e 'ngoe le e' ngoe ea maemo, litekanyetso tsa boitšoaro ba thobalano li ile tsa hlahlojoa mme liphapang tsa sehlopha li ile tsa khethoa bakeng sa teko e 'ngoe le e' ngoe e sebelisang ANOVA ea mekhoa e 'meli (lintlha: Meth / Metsoako ea letsoai, boemo. Pearson χ2 Ts'ebetso e sebelisitsoe ho bapisa liphapang lipakeng tsa lihlopha liperesente tsa ba batona ba bonts'ang likhakanyo, ho kenella, kapa ho nyamela kahare ho tšubuhlellano e 'ngoe le e' ngoe.

Sebaka se khethiloeng sa sebaka

Ho leka hore na kalafo ea pele ho nako ea Meth e amme moputso oa Meth kapa boitšoaro ba thobalano, liteko tsa CPP li ile tsa etsoa. Lisebelisoa tsa likarolo tse tharo (Med Associates) tse nang le likamore tse peli tse kholo tsa kantle (28 × 22 × 21 cm) tse nang le matšoao a khethollang a bonoang le a bonolo mme li arotsoe ke lekareche le lenyane le bohareng (13 × 12 × 21 cm), le sebelisitsoe bakeng sa liteko tsohle tsa CPP . Menyako ka mahlakore ka bobeli a kamore e bohareng e ne e arola likamore, mme e ne e ka phahamisoa ho lumella ho tsamaea ha liphoofolo ka bolokolohi ho lisebelisoa tsohle, kapa ea theoha ho li fella sebakeng se itseng. Lisebelisoa li ne li e-na le li-photobeams ho lekanya nako e sebelisitsoeng kamoreng ka 'ngoe. Letsatsing la pele, ho ile ha etsoa boiteko ba metsotso e 15 ho tseba hore na phoofolo e khetha kamore efe ea pele, eo phoofolo e ngoe le e ngoe e neng e lumelloa ho itsamaela ka bolokolohi lipakeng tsa likamore tsa lisebelisoa tsa CPP. Ha ho likhetho tsa bohlokoa bakeng sa kamore efe kapa efe tse fumanoeng lipakeng tsa lihlopha tsa liteko. Liphoofolo li ne li sa kenyelelitsoe thutong haeba li ne li bontša khetho e atolositsoeng ea phapusi e itseng (phapang e fetang li-120 s; e bontšitsoeng ke <10% ea lithuto). Boemo bo ile ba etsoa matsatsing a 2 le 3. Nakong ea maemo, kamore ea pele e neng e sa khethoe (kamore e kopaneng) e ne e kopantsoe le taolo ea moputso bakeng sa 30 min. Kamore e neng e khethoa pele (kamore e sa sebetsoang) e ne e kopantsoe le taolo ea taolo. Taelo eo liphoofolo li pepesitsoeng ka eona likamoreng tse kopaneng le tse sa sebetsoang e ne e lekana le sehlopha ka seng sa liteko. Tlaleho ea morao-rao e neng e ts'oana le ts'ebetso ea boikaketsi e entsoe ka letsatsi la bone le la ho qetela.

Leka 1.

Taba ea pele, likhoto tsa banna tsa 50 li ne li tloaetse ho kenngoa ka ente ea letsoai bakeng sa matsatsi a mararo a latellanang mme ba batona ba bile le boiphihlelo ba thobalano nakong ea likopano tse tharo. Sebokeng se seng le se seng sa ho emisa, liphoofolo li ne li kenngoa ka 1 mg / kg Meth kapa 1 ml / kg saline (sc), e kentsoeng mekotla ea liteko, mme, 30 min hamorao, e lumelletsoe ho nyalana le mosali ea amohelang ho fihlela ejaculation kapa 1 h. Methati ea boitšoaro ba thobalano e ile ea tlalehoa mme ea hlahlojoa (bakeng sa tlhaloso, bona Boitšoaro ba thobalano, kaholimo). Bekeng e le 'ngoe hamorao, liphoofolo li ile tsa abuoa ka lihlopha tse' ne tsa tlhahlobo tse lekantsoeng bakeng sa kalafo ea lithethefatsi le ts'ebetso ea thobalano bakeng sa tlhahlobo ea CPP. Nakong ea maemo, banna ba ne ba kenngoa ka Meth kapa saline (e tšoanang le kalafo ea lithethefatsi) le 30 min hamorao ba ile ba lumelloa ho nyalana ho fihlela ejaculation. Motsotso o le mong ka mor'a ho omisoa, phoofolo e ile ea kenngoa ka phapusing e kolobelitsoeng. Kamore e sa abeloang e ne e amahanngoa le ente (Meth kapa saline) kapa mating ntle le ente. Kamora ho lateloa, tlaleho ea liphetho (liperesente tsa nako e sebelisitsoeng ka phapusing e kolobelitsoeng nakong ea botle le bo morao; e baloa joalo ka nako e sebelisitsoeng kamoreng e paired e arotsoeng ke nako ka kamore e sa lefelloeng + x 100) le lintlha tsa CPP (Teko ea 1; phapang ka Nako e sebelisitsoeng ka kamoreng e haheletsoeng ka nako ea boikhathollo ba morao-rao e ne e balloa sehlooho se seng le se seng. Lintlha tsa boikhethelo li bapisitsoe le lihlopha tsa liteko tse sebelisitsoeng ka paired t liteko le lintlha tsa CPP li ile tsa bapisoa lipakeng tsa lihlopha tsa liteko tse sebelisang tsela e le 'ngoe ANOVA le teko ea phapang ea bohlokoa ea Fisher bakeng sa post hoc lipapiso, kaofela ka maemo a ts'epo ea 95%

Leka 2.

Ho lekola hore na litlamorao tsa ho bolaoa ke Meth ho CPP bakeng sa Meth kapa mating ho ne ho ipapisitse le ho pepesetsoa nako e le 'ngoe ho Meth le ho nyaloa kapa ka lebaka la Meth feela, ho ile ha etsoa tlhahlobo e eketsehileng. Liraka tsa banna li amohetse Meth (1 mg / kg) le ho ts'oaroana ka nako e le ngoe bakeng sa matsatsi a 4 a latellanang (n = 10). Lihlopha tse peli tsa taolo li ile tsa lula li sa kopanele thobalanong mme li amohetse Meth kapa saline (n = 10 ka 'ngoe). Beke hamorao, CPP ea Meth e ile ea etsoa. Ba batona bohle ba ile ba fumana ente ea Meth ka kamoreng e paired mme ente ea saline e ne e amahanngoa le kamore e sa abeloang. Lipalo tsa likhetho li ile tsa baloa le ho bapisoa ka har'a lihlopha tsa liteko tse sebelisitsoeng ka paired t liteko tse nang le bohlokoa ba 0.05.

Leka 3.

Ho lekola hore na ho ba le nako le nako ho pepesehela Meth le mating ho bohlokoa bakeng sa moputso o fetotsoeng oa thobalano, ho ile ha etsoa thuto ea CPP. Likhoto tsa banna li fumane Meth (1 mg / kg) kapa saline ka nako e ts'oanang le ea mating matsatsi a mane a latellanang (n = 10 ka 'ngoe). Beke hamorao, CPP bakeng sa boitšoaro ba thobalano e ile ea lekoa. Ba batona bohle ba ile ba beoa ka kamoreng e katiloeng ka mor'a ho tlolelana 'me ha ho kopane e neng e hokahane le kamore e sa abeloang. Lipalo tsa likhetho li ile tsa baloa le ho bapisoa ka har'a lihlopha tsa liteko tse sebelisitsoeng ka paired t liteko tse nang le bohlokoa ba 0.05.

Boemo bo hlohlontšitsoeng sebakeng

Ho leka ho bona hore na Meth exposure e fetoloa ke ho kula ho bakoang ke ts'oaetso ea LiCl, ho ile ha etsoa tlhahlobo ea boemo bo hloahloa ea boemo bo itseng (CPA). Tlhahlobo ea CPA e entsoe nakong ea halofo ea pele ea nako e lefifi e sebelisa lisebelisoa tse tšoanang le tse sebelisitsoeng bakeng sa liteko tsa CPP (bona boemo ba boikhethelo ba sebaka, ka holimo). Bakeng sa matsatsi a mararo a latellanang, likhoto tsa banna li fumana boiphihlelo ba thobalano ka nako e le 'ngoe le Meth (1 mg / kg) kapa saline (n = 10 ka 'ngoe). Bekeng e le 'ngoe hamorao, banna bohle ba ile ba fumana ente ea LiCl (10 ml / kg, ip) e pentiloeng le kamore eo pele e neng e ratoa, ha tekanyo e lekanang ea letsoai e ne e amana le kamore eo pele e neng e sa khethoa. Kamora tse morao-rao, bolela lintlha tsa ho khetha (liperesente tsa nako e sebelisitsoeng ka phapusing ea ho paka ka nako e ntle le ea morao-rao; e lekantsoe nako e sebelisitsoeng ka kamoreng e lipakeng e arotsoeng ke nako ka kamore e sa phuthoang + X 100) le CPA lintlha (phapang e sebelisitsoeng nako ho kamore e katiloeng nakong ea morao-rao ka morao ho ho feta e ile ea baloa bakeng sa sehlooho ka seng. Lintlha tsa boikhethelo li bapisitsoe le lihlopha tsa liteko tse sebelisitsoeng ka paired t liteko, ha lintlha tsa CPA li ne li bapisoa pakeng tsa lihlopha tsa liteko tse sebelisang ho sa lefelloeng t liteko, kaofela ka bohlokoa ba 0.05.

Results

Boitšoaro ba thobalano

Meth e amme haholo ho qaleha ha boitšoaro ba thobalano ha ho nyaloa ho ile ha lekoa metsotso ea 30 kamora ho ente ea morao-rao ea lithethefatsi. Phello ena e ne e lekantsoe ke litekanyetso ho 2 mg / kg, empa eseng 1 mg / kg, Meth. Meth e eketsehile haholo litheko le ho kenella hanyane ka hanyane (p = 0.001 le 0.002, ka ho latellana) ha li bapisoa le taolo ea saline (Feie. 1A). Meth ha ea ka ea ama liperesente tsa banna ba neng ba qala boits'oaro, le 100% ea ba batona ba tsoang ka lihlopha tsohle tse tharo tsa kalafo. Meth ha a ka a ba le litlamorao tsa nako e telele ho qaliso ea boitšoaro ba thobalano, joalo ka ha banna ba Meth ba iketselitseng ba sa bonts'a mokhoa o fetotsoeng oa ho ts'oaroa ha o bapisoa le taolo e etselitsoeng letsoai ha ho nyaloa ho ne ho lekoa matsatsing a ho tlohela lithethefatsi 1 le 7 (Feie. 1B,C). Kamora nako, Meth ha e a ka ea ama ts'ebetso ea thobalano ka nako efe kapa efe kaha ho ne ho se na litlamorao ho latsoa ho ejaculation (Feie. 1) kapa linomoro tsa litefiso le litefiso (data e sa bontšitsoeng). Kahoo, Meth e qobellehileng ho qaleha ha ts'oaetso ha e ne e lekoa kamora nakoana ea tsamaiso, empa e sena liphello tsa nako e telele ho susumetsong ea thobalano kapa ts'ebetsong.

Setšoantšo sa 1. 

Litlamorao tsa ho pheta-pheta Mets'ebetso ea thobalano. A-C, Latitude to Mount (ML), intromission (IL), le ejaculation (EL) tsamaiso e latelang ea 0, 1, kapa 2 mg / kg Meth 30 min kamora ho ts'oaroa ka ente ea bosupa le ea ho qetela ea lithethefatsi (A) le matsatsi a thibelo ea lithethefatsi 1 (B) le 7 (C). Lintlha li hlahisitsoe e le mokhoa oa ± SEM. * Phapang ea bohlokoa e tsoang ho ba batona ba kenngoeng ke letsoai (p <0.05).

Ts'ebetso ea locomotor

Methapo ebang ea 1 kapa 2 mg / kg litekanyetso li eketsa ts'ebetso ea locomotor ha e bapisoa le taolo (p <0.001, 1 le 2 mg / kg; Feie. 2A,B). Tsamaiso e phetoang ea Meth e felletse ka karabelo ea sensomotor e tummeng — banna ba neng ba tsamaisoa 1 mg / kg Meth ba bonts'itse ts'ebetso e kholo haholo ea kamora ho latela ente ea ho qetela ea lithethefatsi ha e bapisoa le ente ea pele (p = 0.042; Feie. 2C). Ka lehlakoreng le leng, 2 mg / kg Meth e ile ea fella ka ho fokotseha haholo ha ts'ebetso ea locomotor ka letsatsi la ho qetela ha e bapisoa le letsatsi la pele (p = 0.009; Feie. 2C), e ka bang sesupo sa keketseho ea boits'oaro bo bobe.

Setšoantšo sa 2. 

Litlamorao tsa ho pheta-pheta Meth ho mosebetsi oa locomotor. A, B, Sebaka se eteloang ke ba batona ba tsamaisitsoeng 0, 1, kapa 2 mg / kg Meth e latelang ea pele (A) le ho qetela (B) Methapo ea methapo. Lintlha li hlahisitsoe e le mokhoa oa ± SEM. * Phapang ea bohlokoa e tsoang taolong bakeng sa lihlopha tsohle tsa kalafo (p <0.05); #phapang e kholo lipakeng tsa 1 mg / kg Meth le taolo feela (p <0.05). C, Karabelo e susumetsang ea methapo e khahlisang. Sebaka se tsamaisoa ke ba batona ba tsamaisitsoeng 0, 1, kapa 2 mg / kg Meth e latelang ente ea Meth ea pele le ea ho qetela nakong ea ho rekota ha 10 min ea ho qetela ea lirekoto tsa ts'ebetso ea locomotor. Lintlha li hlahisitsoe e le mokhoa oa ± SEM. * Phapang ea bohlokoa ho banna ba batona le ba batšehali ba sehlopha se le seng sa kalafo (p <0.05).

Boikutlo bo bobe ba ho qhekella thobalano

Boitšoaro ba thobalano

Nakong ea methapo ea bootsoa ea Meth 1, boits'oaro ba thobalano bo ne bo sa angoe ke kalafo ea 1 mg / kg Meth ka nako e 'ngoe le e' ngoe ea likarolo tse tharo tse latelang ha li bapisoa le ba batona ba letsoai le holimo.Lethathamo 1). Liphetho tsena li tiisa ho haella ha litlamorao tsa lethal dose la Meth mabapi le boitšoaro ba thobalano, leha e sebetsoa tikolohong e le 'ngoe. Ntle le moo, Metsoako ea maiketsetso ha ea ka ea fetola boitšoaro ba thobalano ka letsatsi la pele la paradigm ea boemo (pele LiCl e pairing; Lethathamo 1) kapa nakong ea liteko life kapa life tse teng maemong a lihlopha tsa LiCl-tse sa fuoang. Liphetho tsena li tiisa hore Meth ha a ka a ba le litlamorao tsa nako e telele boitshwarong ba thobalano.

Tafole 1. 

Kakaretso ea boitšoaro ba thobalano

Boitšoaro bo bobe ba ho kopanela liphate

Leka 1.

Ho fapana le moo, kalafo ea Meth e phetseng hantle e ile ea matlafatsa ho batla thobalano ho tlamang. Ka taolo, liphoofolo tse khethiloeng ka letsoai le letšo, li ne li thibela boitšoaro ba thobalano ka mokhoa o hlakileng. Ka ho khetheha, liperesente tse fokotsehileng tsa banna ba banna ba apereng li-LiCl ba neng ba hloella le ho kenella ha ba bapisoa le ba batona ba sa sebetseng letsoai le holimo ba ile ba bonahala ka lekhetlo la botšelela (p = 0.039) teko ea boemo bo phahameng ebile e phehella ka liteko tsa boemo ba 7 (p = 0.005; data e sa bonts'ang) le 8 (p <0.001; Feie. 3B). Phapang e kholo ea liperesente tsa banna ba emisitsoeng e bonahetse pele ho la bone (p = 0.041) teko ea boemo bo phahameng ebile e phehella nakong eohle ea maemo (p <0.001; Feie. 3C). Leha ho le joalo, tšekamelo ea Meth e ile ea ama ho hlekefetsoa ka thobalano, joalo ka ha banna ba Methl ba iketselitseng le LiCl ha ba ka ba fihlela thibelo e kholo ea boitšoaro ba thobalano ho fihlela nyeoe ea ho qetela ea maemo ha e bapisoa le ba batona ba sa sebetseng ba Meth. Haholo-holo, liperesente tsa ba batona ba Meth-des-li-li-Meth-preced tse bontšang Metsoako le kemoko li fokotsehile haholo nakong ea teko ea 8p = 0.03 le p = 0.011, ka ho latellana). Kahoo, Meth pretreatment 2 libeke pele ho ho qala ha maemo e ile ea fella ka boitšoaro bo bobe kapa bo qobelloang ba ho batla thobalano.

Setšoantšo sa 3. 

Litlamorao tsa ho nyaloa ka mokhoa o tšoanang (ho kopanela liphate) le Metharo ea ho qhekella ka thobalano e amanang le thobalano (Teko ea 1). A, Litho tsa liteko li kenyellelitse saline- (Sal) kapa banna ba Meth-prereated ba amohetseng LiCl kamora ho tlolelana (banna ba batang) le saline- kapa ba batona ba Meth-e-ba-masene ba amohetseng saline kamora ho tlolelana (banna ba sa fuoang). Ka letsatsi la bobeli la nyeoe e 'ngoe le e' ngoe, banna ba lipara ba ile ba fumana letsoai 'me ba batona ba sa fepang ba amohela LiCl. B, CPeresente ea banna ba ntseng ba nyoloha (B) le ho hlasimolla (C) nakong ea boitšoaro bo litšila ba ho latela thobalano e latelang Meth e tsoileng nako le nako ka boiphihlelo ba thobalano. * Phapang ea bohlokoa ho tsoa ho ba batona ba sa sokang ba saline-p <0.05); #phapang ea bohlokoa ho tloha ho ba batona ba Mege-pele ba sa bollangp <0.05).

Leka 2.

Litlamorao tsa ho lematsa Meth ka ho hloea thobalano le maemo a tlase ho ne ho its'etleha ho boiphihlelo bo tšoanang ba Meth le boiphihlelo. Haholo-holo, ho hloea thobalano le maemo a neng a le sieo ho ne ho sa amehe ho banna ba nang le thobalano ba amohetseng Meth le boiphihlelo ba ho holisa ka nako e fapaneng (e sa kopaneng). Liperesente tsa ba batona ba Methl-e meng ea li-Meth e entsoeng ka mebala e neng e bonts'a likhoto tse kholo le tse ncha li ne li sa tšoane le tse tona tse itlhommeng pele tsa li-saline (Feie. 4). Lintlha tsena li fana ka maikutlo a hore setsoalle sa pele pakeng tsa Meth le boiphihlelo ba thobalano e ne e le sesosa sa litlamorao tsa Meth mabapi le boits'oaro bo matla ba thobalano.

Setšoantšo sa 4. 

Litla-morao tsa ho se kopane ha thobalano (thobalano) le Metharo ea ho qhekella ka thobalano e amanang le thobalano (Teko ea 2). Peresente ea banna ba ntseng ba nyoloha (A) le ho hlasimolla (B) nakong ea LiCl e nang le maemo a holimo a boitšoaro bo bobe ba ho ts'oasa thobalano e latelang Meth e sa amaneng le boiphihlelo ba thobalano. Lihlopha tse peli li kenyellelitsoe: LiCl-paired e entsoeng ka letsoai le LiCl-paired e entsoeng ka Meth.

Boemo bo hlohlontšitsoeng sebakeng

Liteko tse ling tsa taolo li ile tsa senola hore ho sitoa ho thibela ho emisoa ha Meth ha ho natefeloe ha ho bakoe ke tlhalohanyo e sa utloahaleng ea bokuli bo amang LiCl, hobane banna bohle ba thetsitse kamore e amanang le tekanyetso e le 'ngoe ea LiCl. Ka ho khetheha, ba batona ba ba saline- le Meth ba sebelisang nako e fokolang haholo kamoreng ea ho roaloa ka li-LiCl nakong ea morao-rao ha ba bapisoa le boiketsi.p = 0.037 le 0.045, ka ho latellana; Feie. 5A). Ntle le moo, phapang ea nako e sebelisitsoeng ka kamoreng e katiloeng ka li-LiCl kamora hore e nkoe e le ea morao-rao e ne e tšoana hantle le lihlopheng tse ikhethileng tsa Meth- le saline (Feie. 5B).

Setšoantšo sa 5. 

Ditlamorao tsa ho tlolelana ha thobalano (botona le botšehali) le Metso ea ho itšunya-tšunya ha LiCl e thehiloe CPA. A, B, Chelete ea likhetho (Nako e sebelisitsoeng ka kamoreng e marang-rang e arotsoe ke nako ka kamore e sa abeloang + x 100; A) le CPA lintlha (phapang e sebelisoang ka kamoreng ea ho penta nakong ea pele-pele ho feta pele; B) ho banna ba mathe ba tloaetseng ho etsa joalo ka saline (Sal; thobalano + saline) kapa Meth (thobalano + Meth). Lintlha li hlahisitsoe e le mokhoa oa ± SEM. * Phapang ea bohlokoa e tsoang ho boqhetseke sehlopheng se le seng sa liteko (p <0.05).

Sebaka se khethiloeng sa sebaka

Leka 1

Boithuto bo ikemetseng bo senola hore ts'ebeliso ea Meth e ntlafatsa thabo ea thobalano mme ke sepheo sa mantlha sa tšebeliso ea lithethefatsi (Semple et al., 2002; Schilder et al., 2005; Green le Halkitis, 2006). Keketseho ena e susumetsoang ke Meth ea boithabiso ba thobalano ha e so lekoa ka mokhoa oa serope. Ka hona, CPP paradigm e ne e sebelisetsoa ho lekola hore na boitšoaro ba thobalano le Meth bo na le moputso o fetang oa ho ts'oaroa kapa tsamaiso ea Meth feela. E lumellana le lithuto tse fetileng (Agmo le Berenfeld, 1990; Pfaus le Phillips, 1991; Tenk et al., 2009)) ho nyaloa ha banna ba laoloang ke letsoai ho felletse kaPPP-banna ba qetile nako e eketsehileng kamoreng ea ho roala moriri + ka metsi ho feta kamoreng e katiloeng ka letsoai nakong ea morao-rao (p = 0.001; Feie. 6C,D). Ntle le moo, banna ba laoloang ha baa ka ba etsa khetho bakeng sa kamore e 'ngoe ea matsoho + e kopantsoeng le bongata, ho bontša hore ente ea saline pele e emeloa ha e ame moputso oa thobalano (Feie. 6C,D). Liphetho li bonts'itse hore Meth e eketsa CPP bakeng sa thobalano ha e bapisoa le ho nyaloa kapa Meth feela. Ba batona ba qetile nako e eketsehileng nakong ea thobalano ka kamoreng ea thobalano le Meth-ho feta kamoreng e bapalang ka likamano tsa botona le botšehali.p <0.001; Feie. 6C) kapa kamore e nang le Meth-paired (p = 0.02; Feie. 6C), kapa ho bapisoa le sehlopha sa taolo (p = 0.002 le 0.05, ka ho latellana; Feie. 6D). Ka hona, boitšoaro ba thobalano bo kopanetsoeng le Meth bo bonahala bo le monate ho feta boits'oaro ba thobalano kapa Meth e le 'ngoe liphoofolong tse neng li entsoe ka boitšoaro ba thobalano le Meth ka nako e le ngoe.

Setšoantšo sa 6. 

Litlamorao tsa ho tlolelana ha setho sa botona kapa botšehali ka thobalano le Meth tse tlatselletsang ho phallo ea botona le botšehali (Methati e khothalletsoang ea CPP (boits'oaro ba 1). Lihlopha tse 'ne li kenyelelitsoe. A, Lihlopheng tse peli li amohetse tšebetso ea thobalano + (sal) ea kalafo le kalafo e latelang ka phapusing e kolobelitsoeng / e sa ts'oaroang: thobalano + letsoai / thobalano, thobalano + letsoai / letsoai. Sehlopha sa pele se sebelisitse taolo e mpe, kaha letsoai le ne le sa lebelloa ho fetola CPP bakeng sa thobalano. Sehlopha sa bobeli se sebelitse e le taolo e ntle, kaha thobalano e ne e lebelletsoe ho baka CPP. B, Lihlopheng tse ling tse peli ho na le tse ling tse amohetseng likamano tsa botona le botšehali + tse latelang ka likamoreng tse otisitsoeng / tse sa felloang ka thobalano: thobalano + Meth / thobalano kapa thobalano + Meth / Meth. Taelo eo liphoofolo li ileng tsa pepesetsoa likamoreng tse katiloeng ka eona le tse sa kateloang li ne li hanyetsoa kahare ho sehlopha ka seng sa liteko. C, Chelete ea likhetho (Nako e sebelisitsoeng ka kamoreng e katiloeng e arotsoe ke nako ka kamore e sa phuthoang + X 100). Lintlha li hlahisitsoe e le mokhoa oa ± SEM. * Phapang ea bohlokoa e tsoang ho boqhetseke sehlopheng se le seng sa liteko (p <0.05). D, Lintlha tsa CPP (phapang e sebelisoang kamoreng e katiloeng ka nako ea "pele" ho fetisa botle ka ho fetesisa. Lintlha li hlahisitsoe e le mokhoa oa ± SEM. * Phapang ea bohlokoa e tsoang sehlopheng sa thobalano + sa saline / thobalano (p <0.05).

Leka 2

Ka mor'a moo, ho ile ha etsoa qeto ea hore na boitšisinyo bo tšoanang ba Meth le thobalano bo amme CPP bakeng sa Meth feela ha e bapisoa le kalafo ea letsoai ka phapusing e sa lefelloeng. Ho joalo, ba batona ba Meth-e-ba-ba-ba-monna ea neng a tloaelana le ente e 'ngoe le e' ngoe ea lithethefatsi, ba ile ba khetha kamore ea Meth-paired (p = 0.01; Feie. 7). Ho fapana le moo, ba batona ba neng ba fumana li-sindine khafetsa kapa Meth ka ntle ho moelelo oa boemo ba pele, ha ba a ka ba bontša ho rata kamore ea Meth-paired nakong ea morao-rao.

Setšoantšo sa 7. 

Litlamorao tsa ho tlolelana ha botona kapa botšehali ka thobalano ea Methane ho CPP (liteko tsa 2). Letšoao la ho khetha (nako e sebelisitsoeng ka kamoreng e marang-rang e arotsoeng ke nako ka kamore e sa paeloang + X 100) ho banna ba entsoeng ka letsoai (Sal), Meth, kapa thobalano + Meth. Lintlha li hlahisitsoe e le mokhoa oa ± SEM. * Phapang ea bohlokoa ho tloha ho boiketsi sehlopheng se le seng sa liteko (p <0.05).

Leka 3

Qetellong, ho ile ha lekoa hore na Meth le Metsoako e tšoanang ea ho ikatisa e amme CPP bakeng sa ho nyaloa e le mong. Batho ba batona ba iketselitsoeng pele le Meth le ho ikatisa ha ba a etsa khetho ea boitšoaro ba thobalano, ho bonahatsoa ke khaello ea nako e ngata e sebelisitsoeng ka phapusing ea balekane. Ka lehlakoreng le leng, ba batona ba neng ba phekoloa ka letsoai le mating ba ile ba khetha ho rata kamore e etsoang ka matsoho a botona le botšehali.p = 0.003; Feie. 8). Ka bobeli, tlhaiso-leseling ena e bonts'a hore kamano e pakeng tsa Meth le mating e fella ka tšusumetso e kholo ho Meth ka ho ba sieo le ho ts'oaroha ka nako e tšoanang le Meth, empa e fokolitse litšekamelo tsa ho ikatisa ho ba sieo ha moriana o le sieo.

Setšoantšo sa 8. 

Litlamorao tsa ho tlolelana ha setho sa botona kapa botšehali ka thobalano le boits'oaro ba Meth ho CPP e hohelang (Teko ea 3). Letšoao la ho khetha (nako e sebelisitsoeng ka kamoreng e marang-rang e arotsoeng ke nako ka kamore e sa paeloang + X 100) ho banna ba iketselitsoeng ka thobalano + saline (Sal) kapa thobalano + Meth. Lintlha li hlahisitsoe e le mokhoa oa ± SEM.

Puisano

Boithuto ba hajoale bo ile ba leka litlamorao tsa Metha e pheta-phetoang mabapi le boitšoaro ba thobalano ka ho shebisisa ts'ebetso ea thobalano, ho ts'oaroa hampe kapa ho qobella ho batla thobalano, le ho putsa le / kapa moputso oa Meth. Sephetho sa mantlha thutong ena e bile hore Metha ha a ame boitšoaro ba hae ka thobalano, empa o ile a baka boitšoaro bo qobelloang ba thobalano libekeng tse latelang tsa ho kheloha. Phello ena ea boitšoaro bo qobelloang ho tsa thobalano e ne e itšetlehile ka boiphihlelo bo kopanetsoeng le Meth le mating. Ntle le moo, litlatsetso tse tšoanang tsa Meth le liphatsa tsa lefutso li ntlafalitse moputso oa Meth, empa li fokolitse moputso oa thobalano. Ka bobeli, lithuto tsena li bonts'a hore kamano lipakeng tsa Meth le mating e bohlokoa bakeng sa nts'etsopele kapa polelo ea boitšoaro bo qobelloang ba thobalano le liphetoho meputsong ea thobalano le lithethefatsi.

Metso ea ho ithetsa, ha e kopane 'moho le ho nyaloa, e bile le litlamorao tsa nako e telele holima bokhoni ba mokhoa oa ho hlekefetsa ka thobalano o ka sitisang boitšoaro ba thobalano. Tšusumetso ena e ke ke ea hlalosoa habonolo ke bofokoli ba ho ithuta kapa ba ho hopola, hobane banna ba Meth ba iketselitseng maikutlo ha ba a ka ba supa bopaki ba ho ithuta hampe ka nakong ea CPP kapa li -CLC tse khothalletsoang ho etsa thobalano le bohloeki. Ntle le moo, ha ho na monyetla oa hore taolo e pheta-phetoang ea lethal dose le tlase la Meth e bakile ho senyeha hoa kelello le lefu la neurotoxicity le bonoang kamora ho pepeseha ho sa lekanyetsoang ha litekanyetso tse phahameng tsa Meth ka likoto (Walsh le Wagner, 1992; Friedman et al., 1998; Chapman et al., 2001; Schröder et al., 2003) le batho (Ornstein et al., 2000; Simone et al., 2002; Kalechstein et al., 2003), joalo ka Meth e le 'ngoe ea ho hlonama ka paradigms e sebelisang lethal le tšoanang le lipatlisiso tsa morao tjena ha e ea ka ea sitisa ho ithuta ho amoheloang ke ntho mme ha ea ka ea fella ka neurotoxicity (Marshall et al., 2007). Tlhaloso e 'ngoe bakeng sa ho fumana phoso e sa sebetseng kapa polelo ea ho khesa thobalano e nang le maemo ke tahlehelo ea kutlo ea LiCl. Le ha ho le joalo, liphoofolo li ne li khona ho fumana mokhoa oa ho fetohela kamoreng e neng e entsoe ka pele le LiCl. Ka hona, ba batona ba Meth ba neng ba se na mathata a amanang le kamano kapa ho fokotsa maikutlo ho LiCl kapa bokuli bo susumetsoang ke LiCl. Ho bonahala eka Methati ea boikaketsi e bakile takatso e matla ea thobalano kapa e qobelloang, leha a ithutile litlamorao tse mpe, tse tsamaellanang le litlaleho tsa batho (Frosch et al., 1996; Halkitis et al., 2001; McKirnan et al., 2001; Rawson et al., 2002; Somlai et al., 2003; Green le Halkitis, 2006; Springer et al., 2007).

Ho feta moo, litlamorao tsa Meth le boitlamo ba ho nyalisoa mabapi le boitšoaro bo bobe ba thobalano ha bo hlalosoe habonolo ke moputso o ntlafalitsoeng o amanang le ho tlolelana. Ho fapana le hoo, liphoofolong tse amohetseng Meth e tšoanang le boiphihlelo, ho batla moputso ho amanang le ho tlolelana le liphoofolo ho fokotsehile. Ka hona, ho tlameha ho hlahisoa Tlhaloso e 'ngoe bakeng sa litlamorao tsa Methane e ts'oanang le ho ikhopotsa ho bontšoa ka boitšoaro bo bobe ba thobalano. Phuputso ea morao-rao ea neuroanatomical e tsoang laboratoring ea rona e bontsitse libaka tsa boko moo Meth e ka buisanang le litlamorao ho boitšoaro ba thobalano (Frohmader et al., 2010c). Mona, ts'ebetso ea neural e susumetsoang ke mating kapa Meth e ile ea hlahlojoa ho sebelisoa matšoao a tšebetso a neural a kang Fos kapa phosphorylation ea MAPK, ka ho latellana. Methane le li-neurons tse kopantsoeng tse bokellaneng ka har'a li-nucleus li bokellana, li-amygdala tsa basol, le sebaka sa kahare sa "cortex" sa "methapo"Frohmader et al., 2010c) le ho orbitofrontal cortex (Frohmader le Coolen, 2010). Li-cortice tsa pele le tse potolohileng li khahla haholo kaha li kenya letsoho boits'oarong bo bobe.Kalivas le Volkow, 2005; Kalivas le al., 2005; Lasseter et al., 2010; Winstanley et al., 2010). Ho feta moo, hypoactivity ea libaka tsena tsa boko e hokahane le maemo a mangata a kelello a amanang le tahlehelo ea taolo ea inhibitory (Graybiel le Rauch, 2000; Taylor le al., 2002; London et al., 2005). Lintlha tsena tsa bopaki li fana ka maikutlo a hore Meth a ka sebetsa ho li-cortices tsena tse ka pele ho baka liphetoho tse telele tseo ka nako e 'ngoe a fetotseng boitšoaro bo qobelloang ba thobalano. Tumellanong le sena, liketsahalo tse phahameng tsa boitšoaro bo qobelloang ba thobalano li bontšitsoe hore li feta le mathata a mang a kelello, ho kenyeletsa le ts'ebeliso ea lithethefatsi, ho tšoenyeha le mathata a maikutlo (Bancroft, 2008). Hape, ho se sebetse ka tšebeliso ea lithethefatsi tsa cortices ea medial pele le ea orbitofrontal ho etsoa ka boikarabello bakeng sa taolo e fokotsehang ea taolo (Brewer le Potenza, 2008; Fineberg et al., 2010) le boitšoaro bo eketsehileng bo lebisoang ho tsa thobalano bo shebiloeng ho batho ba bangata ba lemaletseng.Jentsch le Taylor, 1999; Bancroft, 2008). Ka tumellano le sena, litla-morao tsa "medial prefrontal cortex" ho litšoelesa tsa banna li ile tsa fella ka boitšoaro bo qobelloang ba ho batla thobalano molemong oa bohloeki ba thobalano bo sebelisitsoeng lithutong tsa hona joale (Davis et al., 2010).

Patlisiso e fetileng e bontšitse hore taolo e pheta-phetoang ho li-psychostimulants kapa opiates e ntlafatsa moputso o tlisoang ke lithethefatsi joalo ka ha o lekantsoe ke CPP (Lett, 1989; Shippenberg le Heidbreder, 1995; Shippenberg et al., 1996). Ntle le moo, boiphihlelo ba thobalano bo ile ba baka ts'abo e ileng ea latela ea moputso oa d-amphetamine (Pitchers et al., 2010). Phuputsong ea morao-rao, litlamorao tsa Meth le / kapa boiphihlelo ba thobalano ho Meth CPP li ile tsa lekoa tlasa maemo a neng a sa lebelloa ho fella ka ts'ebeliso ea lithethefatsi CPP: tekanyetso e tlase ea Meth, teko ea boemo bo le bong, le liteko nakong ea lefifi la mots'eare ka linako tse ling tsa CPP e tlaase haholo (Webb et al., 2009a,b). Mekhoa e khahlisang ea Metha e phetoang kapa ea boiphihlelo ba thobalano e sebelisitsoeng boithuto ba hajoale ha e ea ka ea baka Methapo ea CPP e ntlafalitsoeng. Leha ho le joalo, Methtso ea ho itšupa nako e tšoanang le ho tlolelana ha liphoofolo e ile ea matlafatsa moputso oa Meth, ho bontša hore kamano ena lipakeng tsa Meth le mating e hlahisitse ntlafatso ea ho batla moputso bakeng sa Meth. Liphetho tsena li hlaha tumellanong le litlaleho tsa batho tsa Meth e eketsehang e batlang ho tsebahatsa thobalano nakong ea Meth e nkang e le sepheo sa mantlha sa ts'ebeliso ea lithethefatsi (Semple et al., 2002; Schilder et al., 2005; Green le Halkitis, 2006). Hajoale ha ho tsejoe hore na ke likarolo life tsa boitšoaro ba thobalano tse bohlokoa bakeng sa kamano lipakeng tsa Meth le mating. Thutong ea hajoale, banna bohle ba tloaetse ho tsoaloa hangata. Leha ho le joalo, seo re se fumaneng nakong e fetileng se fana ka maikutlo a hore likamano tsa sechaba li ka lekana ho etsa boitšoaro bo bobe ba ho batla thobalano (Frohmader et al., 2010a).

Likarolo tse tlase tsa Neural tse ka kopanyeletsang litlamorao tse ntlafatsang tsa methapo ea methapo ea methapo le ho ikatisa ka moputso oa Meth li kenyelletsa li-nucleus accumbens le basolateral amygdala. Liphetoho tse tšoarellang ha nako e ntse e ea dendritic spine density le morphology ho li-accumbens li hlahisoa ke taolo e pheta-phetoang ea lithethefatsi (Brown le Kolb, 2001; Robinson et al., 2002; Li et al., 2003; Robinson le Kolb, 2004) kapa ketsahalo ea thobalano (Meisel le Mullins, 2006; Pitchers et al., 2010), 'me li rehelletsoe ka mokhoa oa ho ikopanya le tšebeliso ea litheko tsa lithethefatsi le ho fana ka maikutlo a boithabiso (Pierce le Kalivas, 1997; Vanderschuren le Kalivas, 2000; Li et al., 2004). Amygdala ea basolateral e bohlokoa bakeng sa ho hopola maemo a susumetsoang a amanang le tšusumetso ea lithethefatsi (Grace le Rosenkranz, 2002; Laviolette le Grace, 2006) hape e kenyelletsa ntlafatso ea moputso le matlafatso (Everitt et al., 1999; Cardinal le al., 2002; Bona, 2002). Matlhare kapa inactivations ea basy ea mahaeng a basolateral thibela ho fumana (Whitelaw et al., 1996) le polelo (Grimm le See, 2000) ea ho khutlisetsoa ka har'a cocaine e nang le maemo. Ho feta moo, liso tsa maqhubu a basolateral amygdala li baka ho fokotseha ho arabela bakeng sa tšusumetso e entsoeng ka lipara ka lijo (Everitt et al., 1989) kapa ho matlafatsa thobalano (Everitt et al., 1989; Everitt, 1990) ka likhoto. Ka hona, ho a khonahala hore liphetoho tsa psychostimulant- le tse tlisoang ke ho ikamahanya le maemo ho tlatsetsang ho bokeng moputso oa Meth.

Sensitend regiments tsa lithethefatsi li bontšitsoe ho tsamaisa boitšoaro ba thobalano. Ho utloa litlatsetso tsa d-amphetamine (liente tsa 10 ka mehla tsa 1.5 mg / kg) e nolofalletsa boitšoaro ba thobalano (Fiorino le Phillips, 1999a,b) le mokhoa oa ho atamela ho tsusumetso ea thobalano (Nocjar le Panksepp, 2002). Boithuto lithupelong tsa basali tse entsoeng ka Meth (liente tse tharo tsa letsatsi le letsatsi tsa 5 mg / kg) li hlahisitse boitšoaro bo eketsehileng ba ho amohela (Holder et al., 2010). Ha ho bapisoa, thuto ea hona joale ha e a ka ea bonts'a litlamorao tsa kalafo ea Meth mabapi le boitšoaro ba thobalano. Litlhaloso tse ka bang teng mabapi le phapang ena li kenyelletsa tekanyetso e tlase ea lithethefatsi e sebelisitsoeng thutong ea hona joale, liteko tse fapaneng tsa khothatso ea thobalano, le phapang ea thobalano (Becker le Hu, 2008).

Boithuto bo mabapi le mefuta ea methapo ea methapo ea methapo bo sa tsoa tsepamisa maikutlo liphapusing tsa ho itlopa lithethefatsi ho etsa lipatlisiso mabapi le ho senyeha hoa boitšoaro ba Meth (Belcher et al., 2008; Izquierdo et al., 2010; O'Dell et al., 2011), liphetoho tsa neuroplastic (Brennan et al., 2010), le neurotoxicity (Moszczynska et al., 1998; Kuczenski et al., 2007; Graham et al., 2008). Morero oa mantlha oa lithuto tsena e ne e le ho fihlela maemo a lithethefatsi tsa plasma ka hara rat e haufi le e fumanoang ke lithethefatsi tsa Meth. Ha ho bapisoa, thuto ea hona joale e bonts'itse hore hang ha letsatsi le letsatsi ho latela ts'ebetso ea methapo e tlase ho lekane ho baka boits'oaro bo tšoarellang ba thobalano. Parthigm ea Meth e tlamang e ne e sa sebelisoe ka mabaka a sebetsang: tekanyetso e kholo ea Meth e senya boitšoaro ba thobalano (Frohmader et al., 2010a) mme basebelisi ba batho hangata ba sebelisa ts'ebetso ea thobalano e ntlafatsa lithethefatsi ho boloka ts'ebetso ea thobalano (Semple et al., 2009). Sepheo sa lithuto tsa morao-rao e ne e le ho etsa lipatlisiso tsa moputso oa thobalano le ho ts'oaroa ka matla ho liphoofolo tse nang le boits'oaro bo sa lefelloeng. Liphetho li bontša hore boitšoaro bo qobelloang ho tsa thobalano le moputso o fetotsoeng oa lithethefatsi le thobalano li ka bakoa ke ho pepesetsoa lithethefatsi tse tlase hang ka nako e ts'oanang le boiphihlelo ba thobalano mme ha lia its'etleha ho tlatseng litekanyetso tsa ho sithabela hoa methapo bokong.

Ka kopanelo, lithuto tsa hona joale li theha mohato oa bohlokoa o lebisang kutloisisong ea litlamorao tsa boitšoaro bo khothalletsoang ba thobalano le likamano lipakeng tsa moputso oa lithethefatsi le thobalano. Ho feta moo, lintlha tsena li tšoana le tse tlalehiloeng ho batho ba lemalloang ke batho; ka hona, mofuta oa litekanyetso tsa banna o ka sebelisoa ho feta ho lekola limolek'hule le sebopeho sa litekanyetso tsa Meth ka boitšoaro ba thobalano mme li ka kenya letsoho ho tsa kalafo ea lithethefatsi nakong e tlang.

Mongolo o botlaaseng ba leqephe

  • E amohetse August 4, 2011.
  • Tlhahlobo e amohetse September 8, 2011.
  • E amohetse September 23, 2011.

  • Mosebetsi ona o ne o tšehelitsoe ke Institutes ea Canada ea Health Research Grant RN 014705 ho LMC

  • Bangoli ha ba phatlalatse lithahasello tsa lichelete.

  • Lingoloang li lokela ho lebisoa ho Lique M. Coolen, Univesithi ea Michigan, Lefapha la Limolek'hule le Tlhahlobo e Kopaneng, Saense ea Bongaka II, Kamore ea 7732B, 1137 E. Catherine Street, Ann Arbor, MI 48109-5663. [imeile e sirelelitsoe]

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