Mefuta ea liphoofolo tsa lino tse tahang le lithethefatsi (2013)

Rev Bras Psiquiatr. 2013;35 Suppl 2:S140-6. doi: 10.1590/1516-4446-2013-1149.

Planeta CS.

inahaneloang

Ho lemalla lithethefatsi ho na le liphello tse tebileng tsa bophelo bo botle le tsa sechaba Lilemong tsa ho qetela tsa 50, ho na le mekhoa e fapaneng ea mekhoa e 'nileng ea ntlafatsoa ho bontša mekhoa e tobileng ea boitšoaro ba lithethefatsi' me e tlatsetsa haholo kutloisisong ea mokhoa oa neurobiological oa tšebeliso e mpe ea lithethefatsi le lithethefatsi. Lilemong tse mashome a mabeli tse fetileng, ho 'nile ha etsoa mefuta e mecha ea mehlala ho leka ho hapa likarolo tsa' nete tsa boitšoaro bo hlephileng ba lithethefatsi liphoofolong tsa laboratori. Sepheo sa tlhahlobo ea morao-rao ke ho fana ka kakaretso ea mekhoa e tobileng ea ho sebelisa lithethefatsi hampe le ho itšetleha ka eona le ho hlalosa tsoelo-pele ea morao-rao e entsoeng ho ithuta likarolo tse tobileng tsa boitšoaro bo hlephileng ba liphoofolo.

mantsoe a sehlooho: Mefuta ea liphoofolo; ho itšetleha; ho lemalla; lithethefatsi tsa tlhekefetso

Selelekela

Ho lemalla lithethefatsi ke phephetso e kholo ea sechaba, eseng ka lebaka la liphello tsa eona tse amang bophelo bo botle empa hape le ka lebaka la ts'ebetso ea eona ea maemo a sechaba le a molao sechabeng. Tšebeliso ea lithethefatsi ke ts'ebetso ea motho e ke keng ea hlahisoa hape sebakeng sa laboratori ntle le lithibelo tse ke keng tsa qojoa. Leha ho le joalo, likarolo tse ling tsa boitšoaro ba lefu lena li ka khotsofatsoa ka mokhoa o khotsofatsang liphoofolong tsa laboratori. Ka tsela ena, mekhoa e sa tšoaneng e 'nile ea ntlafatsoa ho bontša mekhoa e tobileng ea boitšoaro ba lithethefatsi. 1,2 Monyetla oa ho ithuta mekhoa ena ho liphoofolo e tlatselitse kutloisiso ea motheo oa neurobiological oa ho noa lithethefatsi le tsa mekhoa ea boko e amehang molemong oa moputso oa lisebelisoa tsa psychoactive. Leha ho le joalo, sepheo se seholo sa lipatlisiso tsa tšebeliso e mpe ea lithethefatsi ke ho senola mekhoa ea ho lemala; ka hona, lilemong tse mashome a mabeli tse fetileng, ho 'nile ha etsoa tlhahiso ea mefuta e mecha ho leka ho nka likarolo tse ling tsa' nete tsa boitšoaro bo hlephileng ba lithethefatsi liphoofolong tsa laboratori. 2

Sepheo sa tlhahlobo ea morao-rao ke ho fana ka kakaretso ea mekhoa e tobileng ea ho sebelisa lithethefatsi hampe le ho itšetleha ka eona le ho hlalosa tsoelo-pele ea morao-rao e entsoeng ho ithuta likarolo tse tobileng tsa boitšoaro bo hlephileng ba liphoofolo.

Mohlala oa botlolo oa mahala

Mohlala oa botlolo oa khetho ea bolokolohi ke mokhoa o sa sebeliseng oa boipheliso oa boipheliso o lebisitsoeng ho tsela ea molomo ea tsamaiso le hangata e sebelisoang lipatlisisong tsa tahi ea joala. Mokhoa ona ha o na thuso, o bonolo, ebile o sebelisa tsela ea tsamaiso eo batho ba e jang ethanol. Mekhoa e itekanetseng ea tsamaiso ea li-ethanol e teng hona joale 'me e hahoa e le mohlala oa batho ba noang lino tse tahang, kaha ba ka khetha ho noa lino tse tahang hammoho le tekanyo ea metsi ka nako ea tlhaho. Mohlala ona o ka sebelisoa ho batlisisa liphello tse khutšoanyane kapa tsa nako e telele tsa ho pepesehela ethanol, hammoho le mekhoa ea methapo ea phekolo ea joala le lithethefatsi. 1 Ho phaella moo, mekhoa ena e ka ba ea bohlokoa ho phekolo ea phekolo ea meriana bakeng sa ho thibela joala ho noa ho tlōla, e leng se bontšang bopaki ba bona bo nepahetseng. 3

Richter le Campbell, 4 in1940, e bile ba pele ho tlaleha hore litoeba tsa laboratori ka boithatelo li ja ethanol. Ba ile ba bontša hore litoeba li fana ka ho noa ha tsona pakeng tsa botlolo ea metsi le botlolo e nang le tharollo ea ethanol e hlahisang, e hlahisitseng tlhahlobo ea bobeli ea botlolo. Tšebeliso e tahang ea joala ka litoeba e atisa ho hlahlojoa ke mokhoa ona, moo ho fumanoang tharollo ea joala le metsi malapeng a bona, moo lijo li fumanehang li adum. Ntle le moo, liphoofolo li ka ba le phihlelo ea metsi ka nako e le 'ngoe le libotlolo tse ling tse' maloa tse nang le libaka tse fapaneng tsa ethanol. Mokhoa oa ho khetha ka bolokolohi, o sebelisang libotlolo tse le 'ngoe kapa tse ngata ho fana ka ethanol, o thusa ho lekanya ho ithaopela le ho ithaopela, ha phoofolo e sa qobellehe ho noa metsi. 5 Ka kakaretso, ho 'nile ha bontšoa hore tšebeliso ea joala e eketseha ha ho hlahisoa palo e phahameng ea mefuta e meng ea joala. 6

Ho lekanyelloa ha lijo tsa ethanol hangata ho etsoang ka metsi a boima le libotlolo tsa ethanol hang ka nako ea lihora tsa 24. Tsela ea ho noa joala e hlalosoa ka mokhoa oa ethanol e kenang ka g ethanol / kg boima ba 'mele / letsatsi,' me karolo ea palo ea metsi a fepa. 7 Leha ho le joalo, liphello tsa ethanol ha li itšetlehe feela ka bokahohle ba ethanol e sebelisoang ke rat kapa mouse ka hare ho lihora tsa 24 empa hape le nako ea nako ea ho noa le mokhoa oa ho noa, e lekanngoang ka tsela e latellanang ka nako e ngata ea mekhoa e metsoako ea ethanol le ka bongata e sebelisoa ka mokhoa oa ho noa. 8 Tšebeliso ea litekanyetso tsena ka bobeli e reretsoe ho felisa mefuta-futa ea liphoofolo ka ho bonahala e le tahi e phahameng ea joala ka lebaka la boima ba 'mele bo fokolang kapa tlhahiso ea metsi e phahameng. 7

Li-rakhoebo tse ithutoang tlasa maemo a ts'ebetso ea ho rarolla likhaliso ka kakaretso ha li noe ho lekaneng ho fumana li-concentrate tsa mali ea ethanol ka holimo ho 80 mg / dL (rats) kapa 100 mg / dL (litoeba), tse ka nkoang ho noa ho tlōla ho likhoto le litoeba . 9,10 Ho bonts'itsoe hore tšebeliso ea ethanol e eketseha ka mokhoa o kenang ka hare. Mohlala oa ho fihlella ka nakoana (nako e 'ngoe le e' ngoe ea 24) ho ethanol ka likhoto e lebisitse ho noa mefuta e phahameng ea ethanol (9 g / kg / day). 11 Boholo ba bopaki bo bontša hore ho lumella ho fumana ethanol ka nakoana ho ka fana ka mokhoa oa mokhoa oa ho ntlafatsa ho ja. 12

Ho noa joala ke taba e 'ngoe e bohloko ka mekhoa ena, kaha maemo a fokolang a ka sebelisoa ka lebaka la tatso ea bona e bonolo le e monate haholo le ea khahloa haholo ka lebaka la tatso ea bona e tsotehang. Ka hona, hangata ho nahanoa hore libaka tsa ethanol tse ka tlaase ho 4% (v / v) li ke ke tsa etsa hore libaka tsa mali li be le matla a holimo ho etsa hore ho be le liphello tse nepahetseng tsa meriana, le hore mokhopolo oa 8-12% ke mokhoa o loketseng oa ho sebelisoa ke litoeba . Ha boholo ba li-rodent hangata ha li noe lihlahisoa tse ngata tsa ethanol, mekhoa e 'maloa e' nile ea etsoa ho koetlisa litoeba ka molomo ho fana ka litekanyo tse ngata tsa lino tse tahang tsa pharmacologically, ho kenyeletsa le ho fana ka likhaello tse phahameng tsa ethanol le thibelo ea nako ea ho qobelloa ho hlahisa ethanol. 1,6

Tsela e 'ngoe ea ho eketsa tšebeliso ea ethanol e akarelletsa ho qhekella ha tharollo ea bohlokoa ka tharollo; sena se ka finyelloa ka ho eketsa monko oa monate o monate, o kang sucrose kapa saccharin, ho tharollo ea ethanol. Mohopolo oa monate o ka lula o le mong kapa o fokotseha butle-butle ka nako ea ho pepa. 12

Ke habohlokoa ho hlokomela hore ho tloha ha 1940 ea morao tjena, mefuta ea litoeba e entsoe ka ho khetha ho hlahisa ethanol e phahameng. Ho tloha ka nako eo, ho na le mefuta e 'maloa ea likhoto le litoeba tse khethiloeng bakeng sa maemo a phahameng a li-ethanol tse phahameng le tse sebelisoang libukeng tse makholo tsa tahi ea joala. 13

Lijo tsa metsi

Thutong ea khale ea Lieber & DeCarli, 14 ethanol e ne e kenngoa ka holimo haholo ho lijo tse nang le phepo e neng e le eona feela mohloli oa phepo e nepahetseng, ho qobella likhoto kapa litoeba ho nka ethanol e nang le lijo. Lijo tseo li ne li ngotsoe ka tsela eo matla a eona a phepo e nepahetseng a neng a hlōla mefuta e mengata ea joala 'me a hlahisa joala ho fihlela 14-16 g / kg / letsatsi.

Phuputsong ea morao-rao e entsoeng ke Gilpin et al., 15 likhoho li ile tsa lumelloa ho fumana libitum ho fihlela 9.2% (v / v) ethanol-ejoang lijo tse nang le 41% ea lik'halori tsa lijo tse tsoang ethanol. Bangoli ba bontšitse hore lijo tsa 9.2% (v / v) tsa joala-liquor e ne e le 79.04 ± 3.64 mL matsatsing 'ohle a teko, e neng e lekana le tlhahiso ea ethanol ea 9.52 ± 0.27 g / kg / letsatsi. Sepheo sa ho noa joala se nang le mali se ne se le 352 mg / dL, se lekantsoe lihora tse peli ka mor'a ho qala ha lefifi la lefifi, le haufi le 80 mg / dL lihora tse 8 kamora ho qala ha leseli. Ka hona, le hoja ho sebelisoa ha lijo tsa metsi ho theoha nakong ea khanya, likhofu li jeoa ka ho lekaneng ho boloka li-pharmacologically li bohlokoa tsa joala ea mali. Ho kenngoa ha ethanol nakong ea lijo-phepo li boetse li khona ho phahamisa likarabo tsa lino tse tahang ha linoko li lekoa nakong ea ho tlohela lijo tsa metsi.

Ntle le bokhoni ba ho hlahisa sehlopha sa linaleli sa matšoao a ho khaotsa ho tsoa ha liphoofolo tse ling tse phelang hantle, 16,17 le ho thusa ho ithuta ho matlafatsa le ho susumetsa libaka tsa ethanol, 15 mokhoa oa ho noa lino tse tahang e le karolo ea lijo tse nang le lithethefatsi tse hlahisang lithethefatsi li etsa hore ho be le lithethefatsi tsa joala tsa mali tse etsisang maemo a bophelo ba meriana mme li lumella liteko tse ngata tsa lithethefatsi tse bakoang ke joala, tse kang lefu la joala la joala le tahiloeng, ethanol le li-solvents tsa indasteri, tse ngata tse atisang ho sebelisoa lithethefatsi le limatlafatsi. 18

Moea oa joala

Mofuta oa mocheso oa ho noa joala o ile oa etsoa ka boiteko ba ho baka boemo ba ho itšetleha ka joala. 19,20 Protocol e sebelisa lithethefatsi tsa mokelikeli oa mokelikeli oa joala tse fumanehang khoebong ho pepesa likhoto kapa litoeba ho mouoane oa ethanol. Ho tsuba ha mokelikeli oa joala ke mokhoa o sa amoheleheng o lumellang hore ho be le tekanyo ea tekanyo ea nako, nako le mokhoa oa ho itlhahisa joalokaha ho khethoa ke experimenter, 'me ha ho lekanyetsoe ke sehlabelo sa phoofolo ho ithaopela ho noa joala. Ha motho a khaotsa ho noa joala, liphoofolo li bontša matšoao a ho mamella le ho itšetleha ka 'mele' me li ka hlahlojoa ka mekhoa e mengata e susumelletsang motho ho susumetsa, ho khaotsa ho mo tlohela le ho itšoara ka nako e telele. 21

Gilpin et al. 15 lipotlolo tse pepenene tsa joala molemong oa lihora tsa 4 le ho lekanyetsa mahlaseli a joala ka boko ba dialysate le likarolo tsa mali tse bokelloang ho tloha monoaneng oa mohatla ka metsotsoana ea 30 nakong ea lihora tsa 4, hammoho le lihora tsa 8 ka mor'a ho khaotsa ho noa joala. Ba fumane hore boholo ba joala bo fumanoang maling le bokoeng nakong ea ho hlahisa mouoane ke 208 ± 15 mg / dL le 215 ± 25 mg / dL ka ho latellana. Likhoeli tse robeli ka mor'a ho khaotsa ho noa joala, lisele tsa mali le boko ba joala li khutlela molaong oa pele oa mouoane, hoo e batlang e le 0%.

Gilpin et al. 15 o ile a boela a pepesa likhoele hore a se ke a phekola mocheso oa joala o tsoelang pele ho bontša boemo ba motho moo ho hlahisoang joala ho leng teng letotong la ho kenngoa ha joala ka mor'a nako ea ho tlohela. Papali e ne e fanoa ka kemiso ea nakoana (ho 6: 00 mantsiboea, ho tloha 8: 00 am) bakeng sa nako ea libeke tsa 4. Ho pepeseha ha nako e telele ho mouoane o kenang mofuteng ho etsa hore ho be le taolo e phahameng ea tahi ho feta tlhahiso ea mouoane e tsoelang pele. 22 Litekanyo tsa joala tsa mali li ile tsa hlahlojoa ka mechine ea moriana oa mohatla, 'me litekanyetso tsa ethanol (mL / h) tse kenang ka kamoreng ea mouoane li ile tsa fetoloa ha ho hlokahala ho boloka lithethefatsi tsa joala boemong ba 125-250 mg / dL. Bangoli ba ile ba sebelisa mekhoa e sebetsang ea ho hlahloba likarolo tse susumetsang tsa ho itšetleha ka joala. Phomolo ea lipapali e ile ea eketsa likarabo tse sebetsang bakeng sa 10% w / v molomo oa molomo ha likhoho li lekoa lihora tsa 6-8 tsa ho tlohela nakong ea matsatsi a tlhahlobo ea mocheso oa mocheso. Liphuputso tse fetileng tse sebelisang mefuta e sa foleng ea mocheso oa joala bo sa foleng li bontšitse hore matšoao a susumetsang a ho itšetleha a teng lintlheng ka nako e boima ea ho tlohela joala, kaha ho pakoa ke boitšoaro bo eketsehileng ba ho tšoenyeha, ho noa lino tse tahang, le ho ba le boikemisetso ba ho tsuba joala kapele nakong ea ho tlohela joala, esita le ha liphoofolo li ntse li e-na le joala maling a tsona ho tloha mofuteng oa mocheso. 21-25 Mefuta eohle ea liphoofolo ea ho itšetleha ka joala, ha e le hantle, ke mefuta e meng ea likarolo tse ling tsa ho itšetleha ka joala.

Mocheso oa motlakase oa mocheso o na le sefahleho se fokolang, kaha liphoofolo li qobelloa ho ja ethanol. Karolo e thahasellisang ka ho fetisisa ea mohlala ona ke ho netefatsa ha eona (mokhoa oa liphoofolo hantle o bolela esale pele mekhoa le mekhoa ea phekolo bakeng sa boemo ba motho). Ka mohlala, acamprosate, e leng lithethefatsi tse thibelang ho khutla ho noa joala ba batho ka ho tlosoa ka takatso ea takatso, ka katleho e thibela ho noa lino tse tahang ka likhoto tse entsoeng ho itšetlehile ka joala ka mocheso oa phallo, empa eseng ka taolo e sa itšetleheng ka eona e sa kang ea hlaseloa ke moholi oa joala. 26

Tšebeliso ea boipheliso

Mokhoa o otlolohileng ka ho fetesisa oa ho lekola matla a matlafatsang a ntho ke ho leka hore na liphoofolo li tla sebetsa (ka kakaretso, sena se bolela ho lever tobetsa) ho fumana ntho eo. Ts'ebeliso ea mefuta ea boitaolo ea lithethefatsi ho ithuta ho lemalla lithethefatsi e ipapisitse le khopolo ea hore lithethefatsi li sebetsa joalo ka tse matlafatsang; ka mantsoe a mang, li eketsa menyetla ea boits'oaro bo lebisang puong ea bona. Kahoo, ho itaola ka lithethefatsi ho nkoa e le karabelo e sebetsang e matlafatsoang ke litlamorao tsa sethethefatsi, mme ke mokhoa o tloaelehileng ho ithuta ho ithaopela ho sebelisa lithethefatsi liphoofolong tsa laboratori. Tlas'a ts'ebetso ena, phoofolo e etsa karabelo, joalo ka ho tobetsa lever, e fanang ka lethal dose. Ho nahanoa hore lithethefatsi li na le ts'ebetso e ts'oanang le tse ling tse matlafatsang - joalo ka lijo - tseo ka tloaelo li ithutiloeng lefapheng la boemo bo sebetsang ba Skinner ho li-1930. 27

Boemo bo sebetsang bo sebelisitsoe e le mohlala oa liphoofolo oa ho lemalla lithethefatsi ho tloha ho 1960s. Libeke 28 e hlalositsoeng, ho 1962, mokhoa oa ho itlhophisa ha morphine ka hare ho rat. Ho tloha ka nako eo, tsamaiso ea boipheliso ea basebetsi e 'nile ea bontšoa bakeng sa heroin, 29,30 cocaine, 31-33 amphetamine, 34 nicotine, 35-37 ethanol, 38-40 le delta-9-THC. 41

Boikarabello ba ho itšehla thajana bo nkoa e le mohlala o ka tšeptjoang ka ho fetisisa le o lekaneng oa tlhahlobo ea lithethefatsi tse matlafatsang liphoofolo. 27 Mokhoa ona o bontša sefahleho se phahameng le ho netefatsa hore ho na le lisebelisuoa tsa lithethefatsi tse matlafatsang. Leha ho le joalo, ho hlahlojoa ha bopaki ba ho itšetleha ha mekhoa ea boipheliso bakeng sa ho lemoha liphello tsa phekolo ea meriana ea phekolo ea lithethefatsi ho fokotsoa ke hore meriana e fokolang haholo e teng bakeng sa morero ona, 'me, hona joale, e batla e le ka ho feletseng ba lekanyelitsoeng feela joala kapa tsuba. 1,27

Lisebelisoa tse sebelisetsoang ho tsamaisa mekhoa ea ho itšireletsa ka lithethefatsi li na le likamore tsa khoebo tse tsejoang e le mabotla a sebetsang kapa Skinner lebokose. Kamore eo e na le lehlakore le nang le lihlahisoa tse ferekanngoa ke phoofolo le ho fetisa karabo e tla etsa hore ho be le pompong ea infusion le ho fana ka tekanyo ea lithethefatsi. Mekhoa e meng e itšetlehileng ka likarabo tse ling, tse kang nose-poking bakeng sa litoeba kapa disk-ho kenyelletsa maeba, e ka boela ea sebelisoa. Ho fana ka lithethefatsi ho ka lokisoa ho bapisa liketsahalo tse ling, tse kang mabone kapa lithane, e le tšusumetso ea khethollo le / kapa li-reinforcers. Meriana ena e atisa ho romeloa ka catheter e kenang ka hare, le hoja litsela tse ling hape li ka sebelisoa, tse kang tsela ea molomo bakeng sa ethanol kapa ho inhalation ea nikotine. 27,36

Ho itaola ka mokhoa o kenang kahare ho kenyelletsa ho kenella ha catheter ka har'a mothapo o moholo. Catheter e fetisetsoa ka tlas'a mokoti mokokotlong, moo e tsoang ka mokhoa o monyane 'me e manehiloe motheong oa polasetiki o ka kenngoang ka har'a sistimi ea marapo. Kamora ho etsoa opereishene, liphoofolo li lumelloa ho fola matsatsi a 'maloa ka masakeng a tsona, ka phihlello ea mahala ea lijo le metsi pele ho ts'ebetso ea maemo. Sekoti siling ea kamore e sebetsang se lumella ho feta le ho tsamaea ka bolokolohi ha catheter e tsitsitsoeng, e hokahantsoeng le pompo e lekanang le pompo ea infusion. 27,36

Karolo ea pele ea mofuta ona ke ho fumana boits'oaro bo sebetsang. Ho fihlela sena, liphoofolo li koetlisetsoa ho matlafatsoa khafetsa moo karabo e 'ngoe le e' ngoe (lever e hatellang) e matlafatsoang ka ho fana ka infusion ea sethethefatsi (intravenous self-administration) kapa lerotholi la tharollo (oral self-administration). Ho fumanoa ha boipheliso ba lithethefatsi ho nahanela mekhoa ea tikoloho le ea meriana. Mohlala, Covington & Miczek 42 ba tlalehile hore palo e kholo haholo ea likhoho tse neng li pepesoa k'hok'heine (15.0 mg / kg ka hare ho intraperitoneally, hanngoe letsatsi ka letsatsi bakeng sa matsatsi a 10) li fumane k'hok'heine ho itlhophisa ho feta liphoofolo tse laolang pele ho letsoalo.

Ho paradigm ea boipuso, ho sebelisoa manane a ts'ebetso ea progressive ratio ho lekola tšusumetso ea ho fumana sethethefatsi. Lenaneo la PR la matlafatso le kenngwa tšebetsong ka keketseho ea palo ea likarabo tse hlokahalang ho fumana phallo ea ts'ebeliso ea lithethefatsi. Mohlala, Richardson & Roberts 43 e hlahisitse algorithm bakeng sa tšelo e 'ngoe le e' ngoe e latellanang ea koae e le hore ho hlahisoe letoto la litlhoko tse ntseng li eketseha tse tla qala ka karo-karolelano ea e le 'ngoe ebe li nyoloha ka potlako e lekaneng hore rat e se ke ea fihlela sekhahla sa karabelo se latellanang nakong ea metsotso e 60, nakong ea hora e 5 nako. Keketseho ea karo-karolelano e ne e le 1, 2, 4, 6, 9, 12, 15, 20, 25, 32, 40, 50, 62, 77, 95, 118, 145, 178… Karo-karolelano ea hoqetela e phethetsoeng, e lebisang ho makhaola-khang infusion, e hlalosoa e le ntlha e robehileng. Tsamaisong ea boipheliso, ntlha e robehileng tlasa kemiso ea PR e bonts'a tšusumetso ea phoofolo ho itlhokomela ka lithethefatsi.

Haufinyane, re sebelisitse kemiso ea PR ho lekola bophahamo bo ka bang teng molemong oa phepelo ea nicotine e kenang ka hare ho liphoofolo e pepesitsoeng khatello ea maikutlo e fapaneng. Kamora mohato oa ho fumana le ho hlokomela, ho itaola ho latela lenane la PR la matlafatso ea lithethefatsi ho ile ha hlahlojoa. Tsoelo-pele ea litlhoko tsa karabelo e latetse algorithm 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26… Likhoto li ne li na le metsotso e 60 ho phethela ka nepo tlhoko e ngoe le e ngoe ea sekhahla. Phallo ea ho qetela e tlisitsoeng e ne e hlalosoa e le ntlha ea tlolo. 36,37 Thutong ea rona, litemiso tsa PR li senoletse ho eketseha ho hoholo ha lintlha tse qhetsoeng lintlheng tseo pele ho pepesetsoeng khatello ea kelello mabapi le litaelo, ho fana ka maikutlo a hore ho pepeseha khatello ea kelello ho ka eketsa tšusumetso ea nikotine ea botho. Lintlha tsena li lumellana le liphuputso tse ling tse bontšang hore ho hlahisa likarolo tse 'nè tsa khatello ea khatello ho eketsa ntlha ea ho tlōla ha cocaine nakong ea PR. 42 Ka mokhoa o ts'oanang, ho 'nile ha bontšoa hore likhoho tse pepesitsoeng ke khatello ea kelello ea maoto li ne li eketsehile PR ho arola lintlha tsa heroine ho latela litaelo tsa tsona. 44

Pholisi ea tsamaiso ea boipheliso e ka boela ea sebelisoa ho lekanyetsa liphello tse matlafatsang tsa lithethefatsi tlasa maemo a ho fihlela nako e telele (lihora tse tloaelehileng tsa 24) lenaneong le tsitsitseng la ho matlafatsa, le tsejoang e le binge. Litholoana tsa laboratori ea rona li bontšitse hore ho noa ka pele ho k'hok'heine ho ekelitse nicotine ka nako ea lihora tsa 24 ea lijo tsa ho itlosa bolutu ba ho itokisetsa ho itokisa. 37

Tsela e kholo ea mekhoa ea boipheliso ke hore li ja nako ebile li theko e tlaase ha li bapisoa le mekhoa e meng. Ho phaella moo, lipatlisiso tsa nako e telele tse sebelisoang ka litsela tse fokolang li lekanngoa ka nako ea li-catheters tse kenngoeng. 27

Sebaka sa boemo

Ka mokhoa o khethiloeng oa khethollo, liphello tsa lithethefatsi, tseo ho nahanoang hore li nka khato e le tšusumetso e sa amoheleheng (US), li atisa ho kopanngoa le tšusumetso e sa keneleng lehlakore. Ka mokhoa ona, e leng tlhaho ea Pavlovian, tlhahiso ea ho se nke lehlakore e fumana bokhoni ba ho sebetsa e le boikutlo bo ts'oanelang (CS). Ka mor'a moo, CS ena e tla khona ho etsa mokhoa oa ho atamela ha lithethefatsi li na le thepa e matlafatsang. Mekhoa e tloaelehileng ka ho fetisisa e sebelisetsoang ho ithuta ho khethoa ka maemo e sebelisa tlhahiso ea tikoloho e le CS le ho boleloa e le sebaka se khethiloeng sebakeng sa boemo (CPP). Lisebelisoa tsa liteko tsa paradigm hangata li na le mabokoseng a nang le likarolo tse peli tse arohaneng, tse arohanngoeng ke menyako ea guillotine, e fapaneng le litekanyetso tsa ts'ebetso. Ka mohlala, likarolo tsena li ka 'na tsa fapana ka fatše,' mala oa lerako, mohlala, kapa litlhaku tse sa tšoaneng. 45 Karolo ea boraro (e sa nke lehlakore) e ke keng ea kopanngoa le lithethefatsi le eona e atisa ho hlaha likarolong. 46

Tsela e tloaelehileng ea protocol ea CPP e na le mekhahlelo e meraro: pele ho boemo ba boemo bo botle, boemo ba boemo bo botle le boemo bo botle ba tlhahlobo (test). Ka mohato oa pele ho boemo, phoofolo e 'ngoe le e' ngoe (rat kapa mouse) e kenngoa ka kamoreng e sa jeleng paate le menyako ea guillotine e tlosoa ho lumella ho fumana lisebelisoa tsohle bakeng sa metsotso ea 15 bakeng sa matsatsi a 3. Letsatsing la 3, phoofolo ena e kenngoa ka lisebelisoa 'me nako e sebelisitsoeng karolong e' ngoe le e 'ngoe e ngotsoe. Bakeng sa mohato oa boemo bo botle, likarolo tsena li aroloa ke menyako ea ho etsa li-guillotine 'me phoofolo e tšoanang e fumana liente tse ling tsa lithethefatsi le koloi ea eona. Meriana ea lithethefatsi e kopane ka kamoreng e khethehileng 'me koloi e kenngoa ka tsela e' ngoe. Kapele ka mor'a hore e mong le e mong a hlajoe, phoofolo e koaletsoe ka metsotsoana ea 30-40 ka kamoreng e tšoanang. Bakeng sa tlhahlobo ea boemo bo botle, phoofolo ena e kenngoa ka kamoreng e sa jeleng paate le menyako ea guillotine e tlosoa ho lumella ho fumana lihlahisoa tsohle. Nako e sebelisitsoeng karolong e 'ngoe le e' ngoe e ngotsoe metsotso ea 15 e hlalosoang bakeng sa mohato oa pele ho boemo; teko e etsoa ka boemo bo se nang lithethefatsi. 46 Ho eketseha ha nako e sebelisitsoeng ka kamoreng e nang le phello ea lithethefatsi ho bontša tsoelo-pele ea CPP, kahoo, phello ea khatello ea lithethefatsi.

CPP e tlalehile lithethefatsi tsohle tse bakang ho itšetleha ka batho; Leha ho le joalo, liphello li matla haholo ho li-opiate le psychostimulants. 45

Lithuto tsa liphoofolo tsa boitšoaro bo hlephileng

Tšebeliso ea mefuta e hlalositsoeng ka holimo e ekelitse haholo kutloisiso ea rona ea motheo oa neurobiological oa ho nka lithethefatsi. Leha ho le joalo, morero o ka sehloohong oa lipatlisiso tsa tšebeliso e mpe ea lithethefatsi ke ho shebana le mekhoa ea ho lemalla lithethefatsi. Ho lemalla lithethefatsi hase feela ho noa lithethefatsi, empa ho hlokomeloa ha tšebeliso ea lithethefatsi ho sa tsotellehe liphello tse bohloko. Ho lahleheloa ke taolo ho fella ka tšebeliso e mpe ea lithethefatsi, ho batla ho sebelisa lithethefatsi ho qobelloa, le ho sitoa ho tlohela tšebeliso ea eona. Ka hona, lilemong tsa morao tjena, ho entsoe boiteko bo matla ba ho sebelisa mokhoa oa ho itlhophisa ho beha mekhoa e tobileng ea boitšoaro bo hlephileng ho fapana le ho phenyekolla feela tšebeliso ea lithethefatsi. Haholo-holo, boiteko bo 'nile ba etsoa ho khetholla hore na litlhahlobo tsa DSM-IV tsa ho hlahloba lithethefatsi tse lemalloang lithethefatsi li ka etsisoa joang liphoofolong. 2

Phuputso ea bohlokoa ea Deroche-Gamonet et al. 47 ke mohlala oa leano lena le lecha la ho batlisisa ka lithethefatsi tsa lithethefatsi. Bangoli ba sebelisitse ho itšireletsa ha cocaine e le hore ba batlisise hore na mekhoa ea ho lemalla lithethefatsi e ka bonoa joang ka litoeba. Ba ile ba bontša hore boitšoaro bo tšoanang le tse tharo tsa bohlokoa tsa ho hlahloba lithethefatsi (ho thatafalloa ho emisa kapa ho fokotsa ho noa lithethefatsi; ho susumetsoa ka ho fetisisa ho nka lithethefatsi, ka mesebetsi e tsepamisitsoeng ka thepa ea eona le thepa ea eona; e etsisitsoeng ka likhoto tse koetliselitsoeng ho itlhokomela ka cocaine.

Ho eketseha ha tšebeliso ea lithethefatsi ke tšobotsi ea phetoho e tsoang ho ts'ebeliso ea lithethefatsi ka linako tse ling ho lemalla. Ho fumana nako e telele ho fumana (ho noa joala, holimo) ho sebelisitsoe haholo ho bontša ho eketseha ha lithethefatsi, haholo-holo ka cocaine le ethanol. Likokoana tse nang le monyetla o atolositsoeng oa ho itšireletsa lithethefatsi butle-butle li eketsa lijo tsa tsona ka nako e telele, ka mokhoa o sa amanang ka ho toba le mamello. Ka mohlala, likhooe tse nang le phihlelo e atolositsoeng (lihora tsa 6 / letsatsi) bakeng sa cocaine ea boipheliso li ile tsa eketsa lijo tsa cocaine ka matsatsi a mangata, athe ba nang le phihlelo e fokolang ea lithethefatsi (hora ea 1 hora) ba ne ba boloka litekanyetso tse tsitsitseng tsa botho ba lithethefatsi, esita le ka morao likhoeli tse 'maloa tsa teko. 48,49 Ho eketseha ha k'hok'heine ho ntseng ho atolosoa ho fihlela tekanyo e eketsehileng ea lithethefatsi ho itšetlehile ka litlaleho tse 'maloa. 50-52 Li-rats tse bontšitseng hore li-cocaine li itšetlehile haholo ka boipheliso ba tsona li boetse li bontšitse hore ho na le tšusumetso e eketsehileng bakeng sa lithethefatsi, kaha ho pakoa ke lintlha tse eketsehileng tsa palo ea lipampiri tsa PR, 53 e leng se bontšang boitšoaro bo bong ba boitšoaro bo hlephileng.

Ho sebelisa lithethefatsi ho qobelloa ho sa tsotellehe liphello tse bohloko ho boetse ho hlophisitsoe liphuputso tsa pele. Lipatlisisong tsena, boitšoaro ba ho batla kapa ho sebelisa lithethefatsi bo ne bo kopantsoe ka ts'ebetso e mpe. Ka mohlala, Vanderschuren et al. 54 o ile a bontša hore ho kopanya CS (ho tsuba) ha ho e-na le cocaine ho itšunya-tšunya boitšoaro bo hlephileng ba lik'hamphani tse nang le phihlelo e fokolang ea k'hok'heine ea boipheliso, empa eseng ka likhoto tse neng li kile tsa e-ba le nako e telele ea ho fumana cocaine.

Lipatlisisong tsa ho sebelisa moriana oa lithethefatsi, haholo-holo ethanol, ho kenngoa ha tharollo e nang le quinine e utloisang bohloko haholo e sebelisoa e le tšusumetso e matla. 55 Ho phaella ha quinine ho tharollo ea ethanol e neng e kile ea fumanoa ke likhoto bakeng sa likhoeli tsa 3-4 ha ea ka ea fokotsa ho ja ha ethanol ho sa tsotellehe tatso e bohloko ea quinine. 56 Ka ho tšoanang, Lesscher et al. 57 ba tlaleha hore litoeba ha lia ka tsa iphapanyetsa quinine ka mor'a hore li fihle nako e telele (libeke tsa 8) ho ethanol, kaha li ne li noa ethanol e lekaneng ho tsoa libotlolo le ka ntle le quinine ka mahlaseli a mangata.

Bothata ba ho itšetleha ka tšebeliso ea lithethefatsi hape ke tšobotsi ea ho lemalla lithethefatsi; sena se ka ithutoa ka liphoofolo tsa laboratori ka ho hlahloba ho batla lithethefatsi ka mokhoa oa boipheliso ha mochine ona o se o fanoe ka ho arabela mochine oa lihlahisoa ke phoofolo. Ho hanyetsa ho felisoa ha boitšoaro bo sebetsang ho 'nile ha hlokomeloa ka likhoto tse nang le histori ea ho atolosoa ka ho feteletseng ho heroine kapa ho cocaine ho itlhophisa. 47,58

Bokhoba ba tahi bo na le litšobotsi tsa lefu le sa foleng le sa feleng. Ka 'nete, palo e kholo ea batho ba lemaletseng lithethefatsi ba khutlela ts'ebetsong ea lithethefatsi leha ba qeta ho tlohela nako e telele; ka hona, mokhoa oa pele oa ho khutlela mokhoeng hape o bohlokoa thutong ea mekhoa ea ho lemalla. Ka kutloisiso ena, de Wit & Stewart 59 li tlalehile hore li-injection tsa cocaine tseo e seng tsa tlhaho kapa tsa ho hlahisa li-cocaine li boetse li khutliselitsoe boitšoaro bo hlephileng ba ho lema ka morao ka mor'a ho fela ha moetsi oa moetsi. E itšetlehile ka liphetho tsena, ba ile ba etsa tlhahiso ea hore mohlala oa bona oa ho khutlisa o ka sebelisoa ho ithuta lintlha tse amanang le ts'ebetsong ea ho sebelisa lithethefatsi.

Mefuta e 'meli ea liphoofolo e bontšitsoe haholo-holo bakeng sa ho ithuta ho khutlela morao. 60 E 'ngoe e tsosolosoa ea ho itlhophisa. 61,62 Mokhoa oa bobeli oa liteko oa ho ithuta ho khutlela liphoofolong ke ho khutlisetsoa ha CPP. 46,63,64 Mefuta ena ea liphoofolo, liphoofolo li koetlisoa ka lekhetlo la pele hore li fumane karabo e amohelehang, ebe li etsa mokhoa oa ho felisoa ha boitšoaro bona. Hang ha boitšoaro bo felisoa, lits'ebetso tsa liteko (ke hore, ho pepeseha ha lithethefatsi kapa lithethefatsi tse seng tsa lithethefatsi) li behoa 'me li lebisa ho ts'ebetsong ea boitšoaro bo kileng ba matlafatsoa ke lithethefatsi. Ho bonahala eka ho tšoana le sepheo sena le ho khutlela morao ho entse hore mokhoa ona o sebelisoe e le mohlala oa ho khutlela morao hape e le tlhahlobo ea takatso. 60

Karolo e loketseng ea mohlala oa ho khutlisa hape ke hore lisosa tse bakang ho khutlela morao le takatso ea batho li boetse li tlaleha hore li tla tsosolosa ho batla lithethefatsi liphoofolong tsa laboratori. Lintlha tsena li kenyelletsa ho hlahella hape lits'etsing tse amanang le lithethefatsi le lithethefatsi le ho pepeseha ho ba sithabetsang. 65,66

Ho ipapisa le liketsahalo tse sithabetsang ho nkoa e le ntho e ka sehloohong e bakang ts'oaetso ea lithethefatsi. 67,68 Liphuputso tsa pele li bontšitse hore khatello ea kelello e ka tsosolosa kokoana-hloko, k'hok'heine, heroine le tsamaiso ea ethanol. 69-71 Ka ho ts'oanang, lipatlisiso tse 'maloa li bontšitse hore khatello ea khatello ea kelello e etsa hore ho khutlisetsoe ha opioid-, amphetamine-, cocaine, le nicotine-e bakoang ke CPP. 64,71-74

Ho na le bopaki bo utloahalang bo tšehetsang sefahleho sa sebopeho sa ts'ebetso ea ho khutlisa, empa leha e le 'nete ea eona ea ho bolela esale pele kapa ea ho sebetsa ha eona e sebetsang hantle e thehiloe ka botlalo. 60

Lipolelo tse qetellang

Tlhahlobo ena e akaretsitse mekhoa e meng e sebelisetsoang ho hlahloba boikarabelo ba ho hlekefetsoa le ho itšetleha ka boikarabelo. Mefuta ena ea liphoofolo e sebelisoa haholo ho ithuta mekhoa ea neurobiological le ea limolek'hule tsa ho noa lithethefatsi. Ho feta moo, tsoelo-pele ea morao-rao ha ho etsisoa matšoao a ho lemalla lithuto tsa liphoofolo, ho latela mekhoa ea DSM-IV, e fana ka monyetla o thabisang oa ho ithuta li-neural le liphatsa tsa lefutso tsa ho lemalla lithethefatsi. Mekhoa ena e mecha ke lisebelisoa tse ntle tsa lipatlisiso tsa ba phekoloang ho ntlafatsa maqheka a ho sebetsana le mokuli.

Cleopatra S. Planeta ke mofuputsi oa Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

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Litlhaloso: CleopatraS. Planeta, Rodovia Araraquara-Jaú, km 01, CEP 14801-902, Araraquara, SP, Brazil. E-mail: [imeile e sirelelitsoe]

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