Ethanol e behiloe sebaka le ho fetoha ha DFBB Ho latela bocha ba Tsamaiso ea Nicotine e fapaneng ka likhopo Ho bontša mokhoa o phahameng oa ho itšoara ka mokhoa o mocha le tikoloho e sa tloaelehang (2014)

Behav Brain Res Sengoloa se ngotsoeng; e fumaneha ho PMC 2015 Jun 5.

E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:

Behav Brain Res 2014 Apr 1; 262: 101-108.

E hatisitsoe Inthaneteng 2014 Jan 7. doi:  10.1016 / j.bbr.2013.12.014

PMCID: PMC4457313

NIHMSID: NIHMS554276

Eya ho:

inahaneloang

Phuputso ena e bonts'a litlamorao tsa ts'ebetso ea nicotine ea lilemong tsa bocha mabapi le khetho ea joala ea batho ba baholo litlalehong tse bonts'ang ts'ebetso e phahameng kapa e tlase ea boits'oaro tikolohong ea lipale, mme o ile a fumana hore na nicotine e fetotsoe ΔFosB ho ventral striatum (vStr) le preortalal cortex (PFC) hang kamora taolo ea lithethefatsi kapa ka mor'a likhoto tse kholo ea ho ba motho e moholo.

Liphoofolo li ile tsa tšoauoa e le ho bonts'a tšebetso e phahameng ea (HLA) kapa e tlase (LLA) lebaleng le bulehileng ka letsatsi la ho beleha (PND) 31 mme la amohela liente tsa saline (0.9%) kapa nicotine (0.56 mg free base / kg) ho tloha PND 35 -42. Likhetho tsa sebaka sa moea se nang le tšusumetso ea Ethanol-ikiwa e ile ea hlahlojoa ho PND 68 kamora matsatsi a 8 a neng a le maemong a paradigm; ΔFosB e lekantsoe ho PND 43 kapa PND 68. Kamora ho pepesetsoa ha nicotine ea lilemong tsa bocha, Liphoofolo tsa HLA li bontšitse CPP ha e phela ka ethanol; Liphoofolo tsa LLA li ne li sa angoe. Ho feta moo, ho pepesetsoa ha nicotine ea bongoaneng bakeng sa matsatsi a 8 ho ile ha eketsa litekanyetso tsa ΔFosB libakeng tsa maoto ho likhoto tsa HLA le LLA, empa keketseho ena e ile ea tsoela pele ho ba motho e moholo ho liphoofolo tsa LLA feela.

Liphetho li bonts'a hore ho pepesetsoa ha nicotine ea lilemong tsa bocha ho thusa ho theha CPP ea ethanol ka har'a likhoto tsa HLA, le hore maemo a phahameng a ΔFosB ha a hlokahale kapa a lekane bakeng sa ho theha CPP ea ethanol ho ba motho e moholo. Lithuto tsena li totobatsa bohlokoa ba ho lekola boitšoaro ba mofuta oa boitšoaro nakong eo ho khetholloang litla-morao tsa boits'oaro le boloi ba ho hlahella ha nicotine ea lilemong tsa bocha.

Keywords: Tlatsetso, Adolescent, ΔFosB, Ethanol, Nicotine, Moputso

1. Selelekela

Boithuto bo bongata bo bonts'itse hore ho batla le ho tseba lintho tse ngata tse amanang le bophelo bo phahameng ho amana le maikutlo a eketsehang a moputso oa lithethefatsi [1-8]. Bacha ba bontšitsoe ho bonts'a ho batla bocha le ho ithuta ho feta batho ba baholo [9-11], mme litlaleho tse 'maloa li bonts'a hore bacha ba na le monyetla oa ho feta batho ba baholo ho feta bokhobeng ba ho qala ts'ebeliso ea lithethefatsi [12-18]. Kahoo, bacha ba ka hlaseloa habonolo ke litlamorao tse matlafatsang le tse khotsofatsang tsa lithethefatsi tse hlekefelitsoeng, 'me bacha ba nang le maikutlo a phahameng a ho batla maikutlo ba ka emela bongata bo kotsing.

Lithethefatsi tse peli tse sebelisoang haholo ke bacha ke nicotine le joala [19, 20], mme bopaki bo supa hore ts'ebeliso ea nicotine e ama tšebeliso ea lino tse tahang. Boitšoaro ba ho tsuba le ho noa hangata bo ba teng hammoho, hangata ka boits'oaro bo amanang le khafetsa ea a mang [21]. Grant [22] e tlalehile hore batho ba ka bang 29% ba qalang ho tsuba pele ba le lilemo tsa 14 ba itšepa joala 'me 8% e tsoela pele ho sebelisa joala hampe nakong ea bophelo ba bona. Ho feta moo, 19% ea ba qalang ho tsuba lipakeng tsa 14 le 16 ba itšepa joala, ka 7% ea batho bana ba hatelang pele ho ts'ebeliso e mpe ea joala. Ho khahlisang ke hore batho ba sa qaleng ho tsuba ho fihlela ba le lilemo tsa 17 ba halofo ea menyetla ea ho lemalla joala kapa ho tsoela pele ho lemalla. Kahoo, ho tsuba ho tloha bonyenyaneng ke ponelo-pele e matla ea ho noha bophelo bohle, mme ho itšepa joala le tlhekefetso [22].

Ho pepesetsoa ha nicotine ea lilemong tsa bocha ho bontšitsoe ho eketsa litlamorao tse khotsofatsang tsa lithethefatsi tse 'maloa liphoofolong tsa batho ba baholo tse sebetsang, ho kenyeletsoa nicotine, cocaine le diazepam [23-26]. Ho ea pele, Riley et al. [27] e bontšitse hore ho tsamaisoa ha nicotine ho litoeba nakong ea bohlankana, empa eseng ho ba motho e moholo, ho eketsa tlhalohanyo ea ho tlosoa hoa ethanol ha ho lekanngoa le ho ba motho e moholo, mme a fana ka tlhahiso ea hore lilemo tsa bocha li emela nako ea bohlokoa ea ho utloa bohloko ha nicotine e lebisang ho liphetoho kelellong e tsoelang pele ho ba motho e moholo. Mohopolo ona o tšehetsoa ke lithuto tse 'maloa tse bonts'ang hore ho pepesetsoa bongoana ho nicotine ho lebisa boemong ba ho tšoenyeha ka ho ba motho e moholo.28-30]. Ho a khonahala hore ho mamella liphetoho ka mora ho hlahella ha nicotine ea bongoaneng ho kenyelletsa taba ea ho ngola ΔFosB, e bonts'itsoeng ho hlahisa maikutlo a phehellang a tsela ea mesolimbic le ho phahamisa kutloisiso ea thepa ea ts'usumetso ea lithethefatsi tse 'maloa tsa tlhekefetso, ho kenyelletsa le joala [31-34], le eo ho fetella hoa hae tsamaisong ea limbic ho eketsang likhetho tsa lithethefatsi [31, 35]. Ho khahlisang, liphoofolo tsa lilemong tsa bocha li bonts'a keketseho e kholo ho feta ea batho ba baholo ho ΔFosB ho nucleus accumbens (NAcc) ho arabela taolong ea koae kapa amphetamine [36]; litlamorao tsa tsamaiso ea nicotine nakong ea bocha ho ΔFosB ha li so hlahlojoe. Hobane liphoofolo tsa lilemong tsa bocha li bonts'a melaoana ea ΔFosB e amanang le batho ba baholo ka lebaka la lithethefatsi tse hlekefelitsoeng, ba kanna ba ba le tlhoko ea ho hohela ka thabo kamora ho hlahella khafetsa ho feta ho hlahisa batho ba baholo ba pepesitsoeng. Mohopolo ona o tšehetsoa ke liphuputso tse bonts'a hore likhoto tsa bocha tse thehang khetho ea sebaka sa boikhethelo ea nicotine (CPP) kamora ho ts'oaroa ha liente tsa 4 li bonts'a keketseho ea immunoreactivity ea FosB (mofuta oa ΔFosB splice ha oa ka oa lekanngoa ka ho khetheha) sebakeng sa ventral tegmental (VTA), NAcc le preortal cortex (PFC) hang kamora teko ea boitšoaro [37].

Leha ho na le bopaki ba hore lilemo tsa bocha ke nako ea ho ts'oara takatso ea maikutlo le tšebeliso ea lithethefatsi ka lekhetlo la pele, tšebeliso ea nicotine e hokahane le ts'ebeliso e matla ea ethanol, le hore kutloisiso e eketsehang ea lithethefatsi tsa tlhekefetso e amana le ho bokellana ha ΔFosB [31], tšusumetso ea ho pepeseha ha nicotine ea bongoaneng maemong a ΔFosB le litlamorao tsa nako e telele ho moputso oa ethanol ha li hlake. Ka hona, thuto ena: 1) e bonts'a litlamorao tsa tsamaiso ea nicotine ea bongoaneng ho khethollo ea joala ea batho ba baholo litlalehong tse khethiloeng nakong ea bocha ka boits'oaro ba bona ba tikoloho e ncha, ho re, ho bonts'a ts'ebetso e phahameng kapa e tlase ea locomotor; mme 2) e ile ea fumana hore na nikotine e fetotsoe osFosB ho "ventral striatum" (vStr) le PFC ea liphoofolo tsena hang kamora tsamaiso nakong ea bocha kapa ka mor'a likhoto tse holileng ho ba motho e moholo.

2. Mekhoa

Lisebelisoa tsa 2.1

Ethanol e fumanoe ho AAPER Alcohol and Chemical Company (Shelbyville, KY). Li-reagents tsohle tse ling li ile tsa rekoa ho Sigma-Aldrich Life Science (St. Louis, MO) ntle le ha ho boletsoe ka tsela e 'ngoe.

Lintho tsa 2.2

Peō e tona le e tšehali (n = 89) ea likhoto tsa moimana tse behiloeng ka nako (n = 10) li ne li sebelisoa e le lithuto; letsatsi la tsoalo le hlalositsoe e le letsatsi la kamora ho beleha 0 (PND 0). Ho netefatsa nts'etsopele e tšoanang litsing tsohle, matlakala ohle a ile a etsoa liphoofolong tsa 10-12 pups (5-6 males / 5-6 females) ho PND 1, 'me a lula ka malapeng a bona ho fihlela PND 21, ka nako eo liphoofolo li neng li khoesoa le ho beoa matlo ka lihlopha tse ts'oanang tsa thobalano tsa 3 ka mekotla e tloaelehileng ea polypropylene e nang le mealo ea li-coccob. Liphoofolo tsohle li ne li bolokiloe Univesithing ea South Florida ka mocheso le vivarium e laoloang ke mongobo ka 12: 12-hr light-darkjikele (7 am / 7 pm). Liteko li ile tsa etsoa nakong ea mohato oa bobebe, 'me tlhokomelo le tšebeliso ea liphoofolo e ne e le ho latela tataiso e behiloeng ke Setheo sa Tlhokomelo ea Liphoofolo le Ts'ebeliso ea Setsi sa Naha le Setsi sa Naha sa Tataiso ea Bophelo bakeng sa Tlhokomelo le Ts'ebeliso ea Liphoofolo tsa Laboraro. Ho latela tataiso ena, liteko li sebelisitse palo e fokolang ea liphoofolo ka sehlopha se hlokahalang ho fumana lintlha tsa bohlokoa.

Tšoaetso ea 2.3 ea Rehaeveal Reacition ho tikoloho ea novel

Ketsahalo ea locomotor e sebelisitsoe ho supa tloaelo ea boits'oaro ea likhoto ho tikoloho e ncha. Ho etsa sena, ho PND 31, liphoofolo li ile tsa tlosoa ntlong ea tsona ea lapeng 'me tsa beoa ka lebaleng la chitja (100 cm) ka tlasa khanya e itekanetseng (20 lux) bakeng sa 5 min. Sebaka se felletseng (TDM) se tlalehiloe ka bo eona ka kh'amera ea video mme ea e hlahlojoa ho sebelisoa software ea EthoVision (Noldus Information Technology, Leesburg, VA) joalo ka ha ho hlalositsoe [38]. Liphoofolo li ne li thathamisitsoe e le ho bonts'a tšebetso e phahameng ea (HLA) kapa e tlase (LLA) lebaleng le bulehileng le sebelisang leano le arohaneng la mahareng, ka ketsahalo ea pele ea lipontšo karolong e holimo ea 50%, le ea morao ho 50% e tlase e amanang le bona batho ba bolileng [4].

2.4 Nicotine ente

Liphoofolo li fumane liente (sc) tsa phosphate-buffered saline (PBS, 0.9%), kapa nicotine hydrogen bitartrate ho PBS (0.56 mg free base nicotine / kg) hang ka letsatsi bakeng sa matsatsi a 4 kapa 8 ho qala ka PND 35. Motsoako ona oa nicotine o bontšitsoe ho eketsa ho arabela bakeng sa ts'usumetso ea maemo [39, 40] le ho eketsa likhechana tsa karabelo e matlafalitsoeng [41] e bonts'a hore e ea putsa ebile ea tiisa, ebile e sebelisitsoe thutong ea pejana ea lilemong tsa bocha [38]. Bakeng sa ente e 'ngoe le e' ngoe, liphoofolo li ne li tsamaisoa ka ntlong ea bona ea bolulo ka kamoreng e benyang e bobebe, ebe li kenngoa ka mokotleng o mocha o kentsoeng liphahlo tse ncha, o kenngoe ente ebe o khutlela hae.

Khethollo ea Sebaka se Behiloeng sa 2.5

Bakeng sa mehato ea CPP, likhoto li fumane liente tsa nicotine ho tsoa matsatsing a PND 35-42 le 18 kamora ho ts'oaroa ha nicotine ea ho qetela, ho PND 60, liphoofolo (n = 40; 4-5 ka sehlopha) li ile tsa lumelloa ho fihlella mahala ho likamore tse peli tse kopaneng tsa Plexiglas (kamore e 'ngoe le e' ngoe: 21 cm wide × 18 cm long × 21 cm high) e nang le mekhahlelo e fapaneng ea pono (e otlolohileng kapa e otlolohileng metsu e ntšo le e tšoeu) le li-cac tactile (rabara e nang le sandpaper kapa ea sandpaper) bakeng sa mekhahlelo e meraro ea 5. Nako e bolelang e sebelisitsoeng ka lehlakoreng le leng la lisebelisoa e sebelisitsoe ho fumana khetho ea kamoreng e le 'ngoe bakeng sa phoofolo ka' ngoe. Leha phoofolo e 'ngoe le e' ngoe e bontšitse khetho ea mantlha qalong, ho ne ho se na tšekamelo kahare ho baahi ea hore kamore e itseng e khethoe. Matsatsing a latelang a 8, ho tloha PND 61 ho isa 68, paradigm e sebelisang maemo a khethiloeng e ile ea sebelisoa moo liphoofolo li neng li koetliselitsoe ho hokahanya kamore e sa rateheng le litlamorao tse tlisoang ke ethanol. Bakeng sa maemo, phoofolo e 'ngoe le e' ngoe e ile ea amohela ente ea ethanol (17%; 1.0 g / kg, ip) mme kamora moo e ne e koaletsoe kamoreng ea pele e neng e sa khethoe bakeng sa 15 min. Tekanyetso ena le ho kenella hoa ethanol ho bontšitsoe ho theha CPP nakong ea bohlankana42] le ho phahamisa dopamine haholo ho NAcc ea bacha le liphoofolo tse kholo tsa batho ba baholo [43, 44]. Liphoofolo tse laoloang li ne li kentsoe metsotso ea 15 kamoreng eo pele e neng e sa khethoe kamora ho entetsoa ka ente ea saline (0.9%, ip). Ka bobeli liphoofolo tse nang le moea oa ethanol le taolo li ile tsa fumana liente tsa saline pele li koalloa kamoreng eo pele e neng e ratoa ke 15 min letsatsi le leng le le leng. Ka hona, phoofolo e 'ngoe le e' ngoe e ne e fumana lithuto tsa 2 ka letsatsi, e le 'ngoe bakeng sa pele e sa khethoeng' me e le ngoe bakeng sa kamore e ratoang. Taelo ea likarolo tsena e ne e fetoloa ka letsatsi le leng le le leng ebe e etsahala hoseng le thapama, e arotsoe ke bonyane lihora tsa 5. Ka PND 69, lihora tse ka bang 16-18 kamora seboka sa ho qetela sa thupelo, liphoofolo li ile tsa lumelloa ho fihlella mahala likamoreng ka bobeli tsa 5 min mme nako e sebelisitsoeng ka phapusing e ngoe le e ngoe e ne e lekantsoe ho lekola CPP. Palo ea likhetho e ne e baloa ka ho tlosa nako e sebelisitsoeng ka kamoreng ea pele e ratoang ho tloha nakong e sebelisitsoeng ka phapusing eo pele e neng e sa khethoe.

2.6 Western Blot e hlahlobisisa

Bakeng sa litlhahlobo tsa immunoblot, likhoto li ile tsa emisoa ka potlako mme vStr le PFC e qheletse 24 hrs kamora mofuta oa 4th kapa 8th nicotine ka PND 39 kapa 43, ka ho latellana, (n = 32; 4 ka sehlopha) kapa matsatsi a 26 ka mor'a 8th 69 (n = 16; 4 ka sehlopha), e tsamaellanang le letsatsi leo CPP e ileng ea hlahlojoa ka sehlopha se seng sa liphoofolo. Lithane li ile tsa qojoa ka potlako leqhoeng le omileng 'me tsa bolokoa ho −80 ° C ho fihlela homogenized joalokaha ho hlalositsoe [38]. Liprotheine li ile tsa aroloa ke sodium dodecyl sulfate polyacrylamide gel electrophoresis (10% polyacrylamide) mme li fetisetse li-electrophoretically ho li-membrane tsa polyvinylidene fluoride. Lithapo li ne li thibetsoe hora ea 1 ho saline ea Tris-buffered e nang le 0.1% lipakeng tsa 20 le 5% lebese le sa omang. Kamora moo, anti-anti anti [FosB (5G4) #2251, 1: 4000; Cell Signaling, Lithane, MA], e hlahisang mongolo o matla oa ΔFosB [45], e ile ea eketsoa ka tharollo ea thibelo 'me litho tsa maloko li ile tsa kenngoa bosiu bosiu ho 4 ° C. Lihora tse leshome le metso e tšeletseng hamorao, likarolo tsa tsona li ile tsa hlatsuoa tsa ba tsa kenngoa ka sekhukhu ka anti -buzi ea poli IgG-HRP, 1: 2000, Santa Cruz Biotechnology, Inc., Santa Cruz, CA] tharollo ea thibelo ea hora ea 1 mochesong oa kamore, le matšoao pono e sebelisitsoeng ho ntlafatsa chemiluminescence. Kamora ho thibeloa ho thibelo ea mali, li-blots li ile tsa hlobolisoa, tsa thibeloa le ho kenngoa mohanyetsi oa mantlha o lebisitsoeng khahlanong le β-tubulin [H-235, Santa Cruz Biotechnology, Inc., 1: 16,000] e le taolo ea ho laolla. Sehlopha sa 35 / 37 kDa se emelang ΔFosB le sehlopha sa 50 kDa se tsamaellanang le β-tubulin li ne li hlakotsoe letheba ka leng ho sebelisa software ea densitometer le Un-Scan-It gel digitizing software (Silk Science Science, Orem, Utah). Sekhahla sa mahlo sa nakong e fetileng se ne se tloaetse maemo ho ea sampole ka 'ngoe,' me liphetho li hlahisoa e le liperesente tsa taolo e lumellanang letlalong le leng le le leng ho tlosa phapang ho blots.

Lipatlisiso tsa Statistical 2.7

Tlhatlhobo ea lintlha tsa 4 ea phapang (ANOVA) e sebeliselitsoe ho fumana litlamorao ho CPP [(e motona kapa e motšehali) × (HLA kapa LLA) × (tlhahiso ea letsoai kapa ea nicotine) × (saline kapa ethanol conditioning)] le teko ea Tukey e sebelisitsoe post hoc ho netefatsa phapang e kholo lipakeng tsa lihlopha. ANOVA ea 3 e ne e sebelisetsoa ho khetholla phapang lipakeng tsa ΔFosB lipakeng tsa liphoofolo tsa HLA e tona le e tšehali le liphoofolo tsa LLA [(e tona kapa e tšehali) × (HLA kapa LLA) × (saline kapa nicotine)] le teko ea Seithuti e ileng ea etsoa poso hoc ho netefatsa liphapang lipakeng tsa lihlopha. Boemo ba p <0.05 bo ile ba amoheloa e le bopaki ba phello e kholo. Hobane boholo ba sampole lithutong tsena bo ne bo le nyane, ho lebisa ho fokotseng matla a lipalo, boholo ba sephetho (η2ρ) kapa Cohen's D) e ne e ikemiselitse litlhahlobo tsohle le litlamorao tse seng tsa bohlokoa ka boholo ba sephetho se fetang 0.06 (η2ρ) kapa 0.4 (D) ho tlalehiloe.

3. Liphetho

3.1 Boitšoaro bo Ts'oarellang tikolohong ea Novel

Ketsahalo ea locomotor e bonts'itsoeng ke likhoto tsa lilemong tsa bocha lebaleng le bulehileng la 5 min le bonts'itsoe Setšoantšo sa 1. TDM e ne e ajoa hangata (Kolmogorov-Smirnov D = 0.083, p> 0.05), ka liphoofolo tse bonts'ang motsamao o fapaneng lipakeng tsa 4339 le 7739 cm / 5 min. TDM ea bohareng e ne e le 5936 cm / 5 min le phoofolo e le 'ngoe kahare (e bontšitsoeng selikalikoe se bohlooho), e ileng ea tlosoa thutong e tsoelang pele. TDM bakeng sa lihlopha tsa HLA le LLA li ne li fapane haholo [t (86) = 12.15, p <0.05; Cohen's D = 2.56] e nang le TDM ea 6621 TDM ± 71 cm / 5 min bakeng sa liphoofolo tsa HLA le 5499 ± 59 cm / 5 min bakeng sa liphoofolo tsa LLA. Liphoofolo li ne li abeloa lihlopha tsa liteko ho latela boits'oaro ba boits'oaro tikolohong ea lipale ho netefatsa hore lihlopha tsohle li bonts'a ho lekana mesebetsing e bulehileng ea tšimo, hape e na le lipalo tse lekanang tsa liphoofolo tsa HLA le LLA (Lethathamo 1). Ho feta moo, ha ho basali ba 1 ba batona le ba basali ba 1 ba tsoang sethaleng se fanoeng ba neng ba abeloa sehlopha ka seng.

Feie. 1  

Karolelano ea boits'oaro ba bocha ba litoeba tsa bocha ho ba sebakeng sa lipalesa. Ketsahalo ea locomotor ea liphoofolo tse lilemong tsa bocha (N = 89) e ne e ikemiselitse ka ho lekanya bolelele bo felletseng (TDM) lebaleng le bulehileng la 5 min. Liphoofolo li ne li khethollotsoe ...
Lethathamo 1  

Mesebetsi e bulehileng ea novel e bontšitsoeng ke litoeba tsa bocha

3.2 Ethanol CPP ea ho ba Motho e Moholo Kamora Ho Phatlalatsoa ha Nikotine Nakong ea Bocha

Lenaneo la pele la liteko le bonts'a hore na ho pepesetsoa hoa nicotine nakong ea bohlankana ho ne ho eketsa tlokotsing ea litlamorao tse tlisoang ke joala ha e le motho e moholo, mme ba fumana hore na likarabo li ne li its'etleha ho boits'oaro ba litoeba ho tikoloho e ncha. Kamora ho khethoa ha likhoto e le HLA kapa LLA, liphoofolo li fumane liente tsa saline kapa nicotine tse tsoang PND 35-42, 'me CPP ho ethanol e ile ea khethoa ha likhoto e ne e le batho ba baholo ba PND 69. Liphetho li bonts'itsoe Setšoantšo sa 2. ANOVA e bonts'itse tšebelisano e kholo ea tsela ea 3 lipakeng tsa tšebetso e bulehileng ea tšimo (HLA kapa LLA), tlhahiso ea nicotine, le boemo ba ethanol [F (1,19) = 5.165, p <0.05], e nang le matla a bonoang a 0.578 le phello e hakantsoeng boholo (η2ρ) ea 0.214. Ha ho phapang e kholo e ileng ea bonoa pakeng tsa ba batona le ba batšehali e le tšusumetso e kholo kapa tšebelisano le boholo ba phello (η2ρ) e ne e le ka tlase ho 0.06 maemong 'ohle, ho bontša hore phetoho ena e ne e se na tšusumetso e kholo liphellong tse bonoeng Liphoofolo tsa HLA tse pepesitsoeng ke nicotine nakong ea bocha le ho ba le ethanol ha e se e le motho e moholo li bontšitse khetho bakeng sa lekareche le nang le ethanol ha le bapisoa le liphoofolo tsa HLA tse neng li pepesitsoe ke nicotine le letsoai le letsoai kapa letsoai le pepesitsoe le ethanol condition [p <0.05]. Nicotine e pepesitse liphoofolo tsa LLA li bonahala li bontša ho hloea phapusing e nang le marang-rang ha e bapisoa le liphoofolo tse pepesitsoeng tse nang le letsoai tse nang le boholo ba phello (Cohen's D) ea 0.80, empa phello ena ha ea ka ea fihlela bohlokoa [t (7) = 1.346, p> 0.05] ka matla a bonoang a 0.425. Kahoo, tlhaiso-leseling e bonts'a hore bacha ba HLA ba kotsing ea ho fumana moputso oa ethanol o ka etsoang, kapa oa qalisoa, ke ho pepesetsoa ha nicotine ke bacha, ha LLA le letsoai li pepesa liphoofolo tsa HLA li hlahisa likarabo ho ethanol e tloaelehileng ea likhoto tsa batho ba baholo [42, 46].

Feie. 2  

Litlamorao tsa ho pepeseha hoa nicotine ea bongoaneng ho khethollo ea sebaka sa ethanol e kentsoeng bathong ba baholo. Likhoto li ne li khethiloe e le ho bonts'a HLA kapa LLA ho PND 31 joalo ka ha ho hlalositsoe, mme ba amohela liente tsa saline (0.9%) kapa nicotine (0.56 mg free base / kg) ...

3.3 ΔFosB nakong ea bocha nakong ea Phatlalatso e Pholohileng ea Nikotine

Hobane keketseho ea ΔFosB meahong ea li-limbic e ntlafatsa khetho ea lithethefatsi [15,16], liteko li fumane hore na ho pepesetsoa ha nicotine ea lilemong tsa bocha ho ba le phello e khethollang maemong a ntho ena e ngotsoeng ho vStr le PFC ho tsoa ho likhakanyo tsa HLA le LLA. Kamora ho khethoa ha boits'oaro, likhoto tsa banna le basali li fumane liente tsa saline kapa nikotine bakeng sa matsatsi a 4 kapa 8 ho qala ka PND 35. Mehlala ea brain e ile ea qheleloa ka thoko lihora tsa 24 kamora ho ente ea ho qetela ho PND 39 kapa 43, ka ho latellana, 'me ea hlahisoa tlhahlobisong ea immunoblot ea Bophirimela. Liphetho tsa litekanyo tsa ΔFosB ho vStr (Setšoantšo sa 3) e bonts'itse phello ea mantlha ea palo ea matsatsi a liente [F (1, 16) = 4.542, p <0.05; η2ρ=0.221] le ho pepeseha lithethefatsi [F (1, 16) = 18.132, p <0.05; η2ρ=0.531] le tšebelisano lipakeng tsa phumaneho ea lithethefatsi le phenotype e atamelang bohlokoa [F (1, 16) = 3.594, p = 0.076; η2ρ=0.183]. Ha ho na phapang ea bohlokoa e hlokometsoeng pakeng tsa ba batona le ba batšehali e le tšusumetso e kholo kapa tšebelisano, le boholo ba phello (η2ρ) e ne e le ka tlase ho 0.025 maemong ohle, ho bontša hore thobalano e na le phello e nyane liphethong tse bonoeng. Matsatsi a mane a ts'oaetso ea nicotine a eketsehile haholo maqhubu a ΔFosB (p <0.05) feela ho vStr ea likhoto tsa HLA, mme keketseho ena e ile ea phehella kamora matsatsi a 8 a tlhahiso ea nicotine, nako eo nicotine le eona e neng e le matla haholo (p <0.05) e eketsehile maemo a ΔFosB ho vStr ho tloha Likhoto tsa LLA. Tlhahlobo ea ΔFosB ho PFC e senotse tšebelisano e kholo lipakeng tsa palo ea matsatsi a liente le ho pepeseha lithethefatsi [F (1, 16) = 7.912, p = 0.05; η2ρ=0.331]. Ha ho na phapang ea bohlokoa e hlokometsoeng pakeng tsa ba batona le ba batšehali e le tšusumetso kapa tšebelisano; leha ho le joalo, ho sebelisana ha thobalano le matsatsi a ente le ho pepesetsoa lithethefatsi ho ile ha atamela bohlokoa (p = 0.055; η2ρ=0.211) le banna ba tloaetseng ho bonts'a litekanyetso tse phahameng tsa ΔFosB kamora matsatsi a 4 a nicotine ho feta basali. Ka kakaretso maemo a ΔFosB ho PFC a ne a sa fetohe kamora matsatsi a 4 a ho pepeseha ha nicotine liphoofolong tsa HLA kapa LLA, empa matsatsi a 8 a ho pepeseha ha nicotine a lebisitse ho keketseho e ts'oanang ea bohlokoa (p <0.5) ho ΔFosB ea lisele tse tsoang ho likhoto tsa HLA le LLA. Kahoo, nicotine e bile le phello ea nako e fapaneng maemong a ΔFosB ho vStr ho tsoa ho likhoto tsa HLA le LLA, empa eseng maemong a PFC.

Feie. 3  

Litlamorao tsa ho pepesetsoa ha nicotine ea lilemong tsa bocha maemong a ΔFosB ka har'a ventral striatum le cortex ea pele. Liroto li ne li khethiloe e le ho bonts'a HLA kapa LLA ho PND 31 joalo ka ha ho hlalositsoe, ba fumane liente tsa saline (0.9%) kapa nicotine (0.56 mg mahala ...

3.4 ΔFosB ea ho ba Motho e Moholo Kamora Ho Phatlalatsoa ha Nikotine Nakong ea Bocha

Ho fumana hore na maemo a phahameng a hlohlelletsoang ke nicotine ho osFosB a hlokometsoe lilemong tsa bocha a ntse a eketseha ka ho ba motho e monyane lilemong, ho latela boits'oaro bo hlophisitsoeng ba likhoto, liphoofolo li fumane liente tsa saline kapa nikotine ka matsatsi a 8 ho tloha PND 35-42, le 27 kamora nako, ho PND 69, VStr le PFC li ile tsa qheleloa ka thoko 'me ΔFosB ea aroloa. Liphetho tsa litekanyo tsa ΔFosB ho vStr (Setšoantšo sa 4) e bonts'itse phello ea bohlokoa ea phenotype ka bobeli [F (1, 16) = 14.349, p <0.05; η2ρ=0.642] le ho pepeseha lithethefatsi [F (1, 16) = 7.368, p <0.05; η2ρ=0.479]. Ka mokhoa o ts'oanang, liphetho tsa litekanyo tsa ΔFosB ho PFC li bonts'itse phello e kholo ea phenotype [F (1, 16) = 9.17, p <0.05; η2ρ=0.534] le ho pepeseha lithethefatsi [F (1, 16) = 10.129, p <0.05; η2ρ=0.559]. Ha ho na liphapang tse hlokometsoeng lipakeng tsa ba batona le ba batšehali e le phello e kholo kapa tšebelisano ea litekanyo tsa ΔFosB ho vStr kapa PFC. Leha ho le joalo, boholo ba phello (η2ρ) bakeng sa phello ea mantlha ea thobalano e ne e le 0.143 le 0.191 bakeng sa vStr le PFC ka tatellano, banna ba batla ho bonts'a litekanyetso tse phahameng tsa ΔFosB ho feta basali. Methati ea ΔFosB e ne e sa fetoloa ho vStr le PFC ea liphoofolo tsa HLA tse amohetseng nicotine nakong ea bocha ha e bapisoa le balekane ba bona ba pepesitsoeng ka letsoai. Ka lehlakoreng le leng, maemo a ΔFosB ka bobeli vStr le PFC ho tsoa likhoto tsa LLA tse fumaneng nicotine nakong ea bocha li ne li le kholo haholo (p <0.05) e kholo ho feta tse tsoang liphoofolong tse nang le letsoai la LLA [vStr t (3) = 2.47, p <0.05; PFC t (3) = 2.013, p <0.05] kapa liphoofolo tse HLA tse kenngoeng ka nicotine [vStr t (6) = 3.925, p <0.05; PFC t (6) = 2.864, le <0.05]. Kahoo, leha matsatsi a 8 a ho pepeseha ha nicotine ea lilemong tsa bocha a lebisitse ho keketseho ea hanghang ea maemo a ΔFosB ho vStr le PFC ho tsoa liphoofolong ka bobeli tsa HLA le LLA, phello ena e ile ea tsoela pele ho ba motho e moholo feela liphoofolong tsa LLA.

Feie. 4  

Litlamorao tsa ho pepesetsoa ha nicotine ea lilemong tsa bocha maemong a ΔFosB maemong a batho ba baholo. Liroto li ne li thathamisitsoe e le ho bonts'a HLA kapa LLA ho PND 31, li fumane liente tsa 8 tsa saline (0.9%) kapa nicotine (0.56 mg mahala ...

4. Puisano

Boithuto ba hona joale bo bonts'a hore ho pepesehela nicotine nakong ea bohlankana ho na le litlamorao tse fapaneng ho CPan ethane le liphetoho lipakeng tsa ΔFosB libakeng tsa maoto le litla tse nang le boitšoaro bo fapaneng tikolohong ea boono. Ho pepesetsoa ha nicotine ea bongoaneng ho thusitse ho thehoa ha ethanol CPP ha e se e le motho e moholo ho liphoofolo feela tse bonts'ang tšebetso e phahameng ea tikoloho ho tsa bohlankana. Ho feta moo, leha ho pepesetsoa ha nicotine ea bongoana ho ile ha eketsa maemo a ΔFosB ho vStr le PFC kamora matsatsi a 8 a tsamaiso, keketseho ena e ile ea phehella ho ba motho e moholo ho liphoofolo feela tse bonts'itseng ts'ebetso e tlase ea tikolohong.

Kahoo, sephetho se bonts'a hore litlamorao tsa ho pepeseha hoa nicotine ea bongoaneng ho CPan ho motho e moholo e ipapisitse le boitšoaro ba liphoofolo, 'me li fana ka tlhahiso ea hore maemo a phahameng a ΔFosB libakeng tse nang le maoto ha a hlokahale kapa a lekaneng ho tsamaisa CPP ea ethanol ho ba motho e moholo.

Ho fumana hore ho pepesetsoa ha nicotine ea lilemong tsa bocha ho nolofalletsa CPP ho ethanol ha e se e le motho e moholo ho liphoofolo tsa HLA ho lumellana le ho fumana hore batho ba nang le boitšoaro bo eketsehileng ba ho tloaelana le tšusumetso ea lipale tse ncha ba bonts'a kutloisiso e kholo ea litlamorao tse tlatselletsang tsa likhomphutha tse hlekefelitsoeng ho feta batho ba nang le ts'ebetso e tlase [1-8]. Leha ho le joalo, ho lokela ho hlokomeloa hore CPP e ka hlahisoa ka matlafatso ea boits'oaro bo itseng nakong ea boemo kapa ka lebaka la litlamorao tsa lithethefatsi tse nang le maemo [47], ka hona, tlhokomeliso e lokela ho sebelisoa ha ho tluoa sephetho sa CPP e le sesupo sa moputso o phahameng oa lithethefatsi. Ehlile, Smith et al. [48] ha a ka a bona ho eketseha ha ethanol ho likhoto tsa Sprague-Dawley ka mor'a ho hlahella ha nicotine ea bongoaneng, a fana ka tlhahiso ea hore thepa e khotsofatsang ea ethanol ha e fetoloe ke boiphihlelo ba pele le nikotine. Leha ho le joalo, bangoli bana ba sebelisitse paradigm e tsoelang pele ea matsatsi a 21 mme ha ba khetholle liphoofolo ho latela ts'ebetso ea locomotor tikolohong ea lipale. Liphetho tsa boithuto ba hona joale li fana ka maikutlo a hore litlamorao tsa li-nicotine tsa letsatsi le letsatsi tsa nicotine li ka fapana le tse hlahisoang ke ho pepeseha hoa nicotine mme li bonts'a bohlokoa ba ho khetholla lipakeng tsa likhahla tsa HLA le LLA, phapang e ka ba ea bohlokoa haholo ha o ithuta lilemong tsa bocha. Leha bafuputsi ba bangata ba tlalehile hore palo ea bacha e ka ba le hloko haholoanyane litlamorao le ho matlafatsang tsa lithethefatsi [49-51], tlhokomeliso ena e kanna ea bonts'a tloaelo ea bongoana ea ho hola ea ho ba le litšobotsi tsa liphoofolo tsa HLA [10]. Ho joalo, liphuputso ho palo ea batho li bontšitse hore lipalo tse batlang takatso ea maikutlo nakong ea bohlankana 'me li fokotseha kamora moo, le ba ntseng ba ts'oana le maikutlo a bocha ba ho batla ho eketsa ts'ebeliso ea joala [52].

Liphetho tse bonts'ang karohano e kholo ea boloi ba nicotine ea bongoaneng ho ΔFosB bokong ho tsoa ho HLA le LLA litheko li totobatsa phapang e teng pakeng tsa lihlopha tsena tsa liphoofolo. Liphetho li bonts'a keketseho e hlakileng ea maemo a ΔFosB ho vStr le PFC ho tsoa lihlopheng ka bobeli tsa likhoto tse latelang matsatsi a 8 a ho pepeseha ha nicotine ea bongoaneng, empa phello ena e ile ea phehella ho ba motho e moholo feela bokong ho tsoa ho LLA likhoto. Soderstrom et al. [53] e bonts'itse hore matsatsi a 10 a pepesehetse nicotine (0.4 mg / kg, ip) ho tsoa ho PND 34-43 e ile ea eketsa ts'oaetso ea FosB ho NAcc ka matsatsi a 37 kamora ho ente ea nicotine ea ho qetela, empa bangoli bana ha ba ka ba lekanya ΔFosB ka kotloloho kapa ba bonahatsa mofuta oa boitšoaro oa phenotype oa le liphoofolo. Liphetho tse bonts'ang hore maemo a phahameng a ΔFosB kamora ho pepesetsoa ha nicotine ea bongoaneng a hlaha feela ho bacha ba LLA ba fana ka maikutlo a hore bacha ba LLA ba "baholo joalo" ho feta balekane ba bona ba HLA. Ho joalo, ho phahamisoa ha nako e telele ha ΔFosB kamora ts'ebetso ea lithethefatsi ho bontšitsoe khafetsa ho liphoofolo tse kholo [31, 33, 34].

Ho ne ho lebelletsoe hore liphoofolo tsa HLA tse pepesetsoeng nicotine nakong ea bocha li bonts'a CPP e kenyellelitsoeng ethanol ho ba motho e moholo le ho phahamisa BFosB ka mokhoa o hlakileng oo ka mokhoa o hlakileng o ileng oa thabisa tsela ea moputso. Leha ho le joalo, liphetho li bontša hore maemo a phahameng a ΔFosB kamora ho pepesetsoa ha nicotine ea bongoana ha ho hlokahale ebile ha a lekane bakeng sa ho thehoa ha ethanol CPP ha a le motho e moholo. Hobane paradigm e khethollehileng ea CPP e sebelisitsoeng thutong ena e amehile ka litlamorao tse tšoenyang tsa ethanol [54, 55], CPP e susumetsoang ke ethanol e hlokometsoeng kamora ho pepesetsoa ha nicotine ea bocha e ka kenella lipakeng tsa liphetoho ho utloeng litlamorao tsa ethanol, ho fapana le sephetho sa tsela e putsoang ea moputso. Liphoofolo tsa batho ba baholo tse pepeselitsoeng nicotine nakong ea bocha li bontša kutloisiso e eketsehileng ea khatello ea maikutlo le matšoenyeho ha e le batho ba baholo, joalo ka ha ho pakoa ke corticosterone e phahameng [28], e fokotse tšibollo ea sebaka se bulehileng sa nov le ho fokotsa nako matsohong a bulehileng a maze a phahameng [29, 30]. Ka hona, ho bonahala eka liphoofolo tse kholo li pepesehetse nicotine ha e le lilemong tsa bocha li ka bonts'a CPP ea ethanol ka paradigm e ts'oanang ka lebaka la thepa e tšoenyang ea ethanol. Ho khahlisang, liphoofolo tse bonts'ang polelo e phahameng ea ΔFosB li kanna tsa se amehe haholo ka khatello ea maikutlo le matšoenyeho joalo ka ha ho bontšoa ke nako e eketsehileng e sebelisoang liatleng tse bulehileng tsa maze e phahameng [56], eketsa nako ea ho sesa litekong tsa ho sesa tse qobelloang tsa li -akilolt [56], ho hloka mamello ho eketsehileng ka mora khatello ea khatello ea sechaba [57] le karabelo e fokotsang ea corticosterone ho khatello ea maikutlo [58]. Kahoo, nicotine e pepesitse liphoofolo tsa LLA, tse bonts'ang polelo ea sustFosB e le batho ba baholo, li kanna tsa se ke tsa fumana litlamorao tsa phello ea ethanol, mme ka lebaka leo, tsa hloleha ho bonts'a CPP ho paradigm e khethollehileng. Ho joalo, liphoofolo tsa LLA tse kenngoeng ke ethanol li bontšitse phokotso e kholo (D = 0.80) ka nako e sebelisitsoeng lehlakoreng la mokokotlo oa ethanol ha e bapisoa le liphoofolo tsa LLA tse kentsoeng letsoai, tse fanang ka maikutlo a ho hlohlona ha ethanol. Lithuto tse ling li hlokahala ho netefatsa phapang lipakeng tsa liphoofolo tsa HLA le LLA ka boitšoaro bo nang le matšoenyeho le maikutlo a sithabetsang kamora ho pepesetsoa ha nicotine ea bongoaneng.

Leha ho ne ho se na phapang e kholo ea lipalo pakeng tsa liphoofolo tse tona le tse tšehali, tse ling li bile le litlamorao tse kholo tse amanang le thobalano. Litekanyo tsa ΔFosB ho PFC li ne li batla li le tlase tsa 25% ho bacha ba banna ho feta balekane ba bona ba basali ba 4, le ka 19% e phahameng ho banna ho feta bacha ba basali ba latelang mananeo a nicotine a 4, a fana ka maikutlo a hore banna ba lilemong tsa bocha ba ka bontša keketseho ea ΔFosB kamora ho pepeseha tse nyane. ho nicotine ho feta basali ba lilemong tsa bocha. Ntle le moo, litekanyo tsa ΔFosB li ne li le 15-17% e phahameng ho vStr le PFC ea banna ba baholo ho feta ho bonoa ho basali ba baholo ho sa tsotelehe hore na liphoofolo tsena li ile tsa pepesetsoa letsoai kapa nikotine joalo ka bacha. Phumano ena ea morao-rao e lumellana le tlaleho e bonts'ang hore banna ba baholo ba bonts'a maemo a hloahloa a osFosB maemong a bokellanang a bokaholimo ba karolo ea mantlha le likhetla ho feta bo-mphato ba bona ba basali mme phapang ena e teng liphoofolong tse kenngoeng ka letsoai kapa cocaine (15 mg / kg) bakeng sa libeke tsa 2 tse bonts'a hore phapano ena e ikemetse ponahalong ea lithethefatsi [45]. Ho tsebo ea rona, ha ho na lipatlisiso tsa liphoofolo tsa bocha kapa tsa batho ba baholo tse ileng tsa hlahloba ho se tšoane ha thobalano ho polelo ea ΔFosB kamora ho hlahella ha nicotine; liphumano tsena li tiisa patlisiso e tsoelang pele.

Ka kakaretso, liphoofolo tsa bocha tse bonts'ang liphapang tsa boits'oaro ba boits'oaro tikolohong ea lipale li bonts'a liphapang ho: 1) litlamorao tsa nako e telele tsa ho pepeseha ha nicotine ho utloeng litlamorao tsa ethanol ha motho e moholo; 2) ho hlahisoa ha ΔFosB nakong ea ho pepesetsoa nikotine khafetsa; le 3) ho phehella ha ΔFosB kamora ho pepeseha ha nicotine khafetsa. Liphuputso tsena li fana ka motheo oa ho batlisisa liphapang tsa bofokoli ba tlhaho ba liphoofolo tsa bocha, litšobotsi tse ka hlahlojoang ho sebelisoa mehato e bonolo ea boits'oaro.

Lintlha-khōlō Tsa

  • Ho pepesetsoa ha nicotine ea bongoaneng ho hlahisa CPP ea joala maemong a phahameng a takatso ea ho batla batho ba baholo
  • Ho pepesetsoa ha nicotine ea lilemong tsa bocha ho eketsa polelo ea ΔFosB
  • Polelo ea osFosB e latelang nicotine ea lilemong tsa bocha e phehella ho ba motho ea moholo ka ho batla maikutlo a tlase

lumela hore baa fokola

Patlisiso e tšehelitsoe ke Naha ea Florida le NIAAA ea Setsi sa Naha sa Bophelo ka tlasa nomoro ea F32AA016449. Likahare ke boikarabello ba lingoli feela mme ha li hlile ha li emele maikutlo a semmuso a State of Florida kapa Institutes of Health ea naha.

Mongolo o botlaaseng ba leqephe

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References

[1] Dellu F, Piazza PV, Mayo W, Le Moal M, Simon H. Ho batla tsebo ka likhoto-litsobotsi tsa boitšoaro le kamano e ka bang teng le semelo se batlang maikutlo ho motho. Boithuto ba Neuropsychobiology. 1996; 34: 136-45. [E fetotsoe]
[2] Deminiere JM, Piazza PV, Le Moal M, Simon H. Tsela ea liteko mabapi le ho ba kotsing ea motho ea lemaletseng ts'ebetso ea psychostimulant. Neurosci Biobehav Rev. 1989; 13: 141-7. [E fetotsoe]
[3] Klebaur JE, Bardo MT. Phapang e fapaneng le e ngoe ea batho ba batlang bocha papaling ea maze ba bolela esale pele hore na sebaka sa maemo a leholimo se tla ba joang. Pharmacol Biochem Behav. 1999; 63: 131-6. [E fetotsoe]
[4] Klebaur JE, Bevins RA, Segar TM, Bardo MT. Phapang e le 'ngoe ea likarabo tsa boits'oaro ho li-novelty le amphetamine boits'oaro litabeng tsa banna le basali. Behav Pharmacol. 2001; 12: 267-75. [E fetotsoe]
[5] Nadal R, Armario A, Janak PH. Kamano e ntle pakeng tsa ts'ebetso tikolohong e ncha le boits'oaro bo sebetsang ba ethanol literekeng. Psychopharmacology (Berl) 2002; 162: 333-8. [E fetotsoe]
[6] Piazza PV, Deminiere JM, Le Moal M, Simon H. Factors tse bolelang esale pele hore motho a ka ba kotsing ea ho iphelisa. Mahlale. 1989; 245: 1511-3. [E fetotsoe]
[7] Zheng X, Ke X, Tan B, Luo X, Xu W, Yang X, et al. Ho ts'oenyeha hoa morphine maemo a sebaka: likamano le tšusumetso e bakoang ke khatello ea maikutlo le boits'oaro bo batlang bo sa tloaelehang litloaelong tsa bacha le tsa batho ba baholo. Pharmacol Biochem Behav. 2003; 75: 929-35. [E fetotsoe]
[8] Zheng XG, Tan BP, Luo XJ, Xu W, Yang XY, Sui N. Tsela e batlang boits'oaro le tšusumetso e nang le khatello ea maikutlo lithutong tsa nako ea bongoana li fapana ka ho fapana le boemo ba sebaka sa morphine botsofaling ba bona. Mekhoa ea Behav. 2004; 65: 15-23. [E fetotsoe]
[9] Crawford AM, Pentz MA, Chou CP, Li C, Dwyer JH. Lits'oants'o tse ts'oanang tsa ntlafatso ea maikutlo le ts'ebeliso e tloaelehileng ea lithethefatsi ho bacha. Psychol Adict Behav. 2003; 17: 179-92. [E fetotsoe]
[10] Philpot RM, Wecker L. Ho theoha hoa boits'oaro bo batlang bocha lilemong tsa bocha mabapi le tšibollo ea karabelo le litlamorao tsa litheko tsa litekanyetso. Behav Neurosci. 2008; 122: 861-75. [E fetotsoe]
[11] Spear LP. Boko ba bongoana le liponahatso tse amanang le lilemo tsa bocha. Neurosci Biobehav Rev. 2000; 24: 417-63. [E fetotsoe]
[12] Anthony JC, Petronis KR. Tšebeliso ea lithethefatsi tsa pele-pele le kotsi ea mathata a morao a lithethefatsi. Lithethefatsi. 1995; 40: 9-15. [E fetotsoe]
[13] Bonomo YA, Bowes G, Coffy C, Carlin JB, Patton GC. Bacha ba lilemong tsa bocha le ho qalella ho ts'epa joala: thuto ea 'mele e nkileng lilemo tse supileng. Ho lemalla. 2004; 99: 1520-8. [E fetotsoe]
[14] Grant BF, Stinson FS, Harford TC. Lilemo qalong ea tšebeliso ea joala le ts'ebeliso e mpe ea joala ea DSM-IV le ts'ehetso: ts'alo-morao ea 12. J Tlhekefetso. 2001; 13: 493-504. [E fetotsoe]
[15] Kandel DB, Yamaguchi K, Chen K. Mekhahlelo ea tsoelo-pele ea ts'ebeliso ea lithethefatsi ho tloha bocheng ho ea ho motho e moholo: bopaki bo bong ba khopolo ea khoro. J Stud Joala. 1992; 53: 447-57. [E fetotsoe]
[16] Lynskey MT, Heath AC, Bucholz KK, Slutske WS, Madden PA, Nelson EC, et al. Keketseho ea ts'ebeliso ea lithethefatsi ho basebelisi ba li-cannabis tsa pele-ho qala vs. Jama. 2003; 289: 427-33. [E fetotsoe]
[17] Patton GC, McMorris BJ, Toumbourou JW, Hemphill SA, Donath S, Catalano RF. Ho kena bohlankaneng le pelehi ea tšebeliso ea lithethefatsi le tlhekefetso. Lingaka tsa bana. 2004; 114: e300-6. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
[18] Taioli E, Wynder EL. Kameho ea lilemo eo ho tsubang ho qalang ho atisang ho tsuba ha e le motho e moholo. N Engl J Med. 1991; 325: 968-9. [E fetotsoe]
[19] Johnston LD, Tonakholo ea O'Malley, Bachman JG, Schulenberg JE. Liphetho tsa naha mabapi le ts'ebeliso ea lithethefatsi tsa bocha: Kakaretso ea liphetho tsa bohlokoa, 2008. Phatlalatso ea NIH; Bethesda, MD: 2009.
[20] Johnston LD, Tonakholo ea O'Malley, Bachman JG, Schulenberg JE. Ho beha leihlo litlamorao tsa naha tsa kamoso ts'ebelisong ea bocha ea lithethefatsi: Kakaretso ea liphetho tsa bohlokoa, 2011. Setsi sa Patlisiso ea Sechaba, Univesithi ea Michigan; Ann Arbor: 2012.
[21] Johnson KA, Jennison KM. Letšoao la ho tsuba-ho tsuba le maemo a bophelo sechabeng. Int J Addict. 1992; 27: 749-92. [E fetotsoe]
[22] Grant BF. Nako ea ho qala ho tsuba le ho kopana ha eona le ts'ebeliso ea joala le ts'ebeliso e mpe ea tahi ea DSM-IV le ts'ehetso: litlamorao ho tsoa ho Patlisiso ea Phihlelo ea Boitšoaro ba Nala ea National Longitudinal. J Tlhekefetso. 1998; 10: 59-73. [E fetotsoe]
[23] Adriani W, Spijker S, Deroche-Gamonet V, Laviola G, Le Moal M, Smit AB, et al. Bopaki ba ho ba kotsing ea ts'ebetso ea neurobehaeveal ea nicotine nakong ea periadolescence ho litoeba. J Neurosci. 2003; 23: 4712-6. [E fetotsoe]
[24] James-Walke NL, Williams HL, Taylor DA, McMillen BA. Pellado ea nicotine ea Periadolescent e hlahisa maikutlo a ho matlafatsa ka diazepam ho rat. Neurotoxicol Teratol. 2007; 29: 31-6. [E fetotsoe]
[25] McMillen BA, Davis BJ, Williams HL, Soderstrom K. Periadolescent nicotine exposalization heterologous sensitization to cocaine matlafatsa. Eur J Pharmacol. 2005; 509: 161-4. [E fetotsoe]
[26] McQuown SC, Belluzzi JD, Leslie FM. Phekolo e fokolang ea nicotine nakong ea bocha e eketsa moputso o latelang oa koae. Neurotoxicol Teratol. 2007; 29: 66-73. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
[27] Riley HH, Zalud AW, Diaz-Granados JL. Tšusumetso ea bongoana bo sa feleng ba nicotine mabapi le ho tebela ha ethanol nakong ea ho ba motho e moholo lilemong tsa litoeba tsa C3H. Joala. 2010; 44: 81-7. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
[28] Klein LC. Litlamorao tsa ho pepesetsoa ha nicotine ea lilemong tsa bocha mabapi le ts'ebeliso ea opioid le likarabo tsa neuroendocrine ho likhoto tsa banna le basali tse holileng. Clin Psychopharmacol. 2001; 9: 251-61. [E fetotsoe]
[29] Slawecki CJ, Gilder A, Roth J, Ehlers CL. Boitšoaro bo ntseng bo eketseha bo tšoanang le litšoelesa tsa batho ba baholo tse pepesitsoeng nicotine e le bacha. Pharmacol Biochem Behav. 2003; 75: 355-61. [E fetotsoe]
[30] Slawecki CJ, Thorsell AK, El Khoury A, Mathe AA, Ehlers CL. Ho eketseha ha ts'oaetso ea CRF joalo ka NPY le litšoelesa tse kang tsa NPY litekong tsa batho ba baholo ho pepesetsoa nicotine nakong ea bocha: kamano e amanang le ho tšoenyeha joalo ka boits'oaro bo joalo. Neuropeptides. 2005; 39: 369-77. [E fetotsoe]
[31] Nestler EJ, Kelz MB, Chen J. DeltaFosB: mokena-lipakeng oa molek'hule oa polasetiki e telele ea neural le ea boitšoaro. Brain Res. 1999; 835: 10-7. [E fetotsoe]
[32] Nestler EJ. Molek'hule ea moea oa ho lemalla. Ke J Addict. 2001; 10: 201-17. [E fetotsoe]
[33] Nestler EJ. Motheo oa limolek'hule tsa polasetiki ea nako e telele e tlatsitsoeng. Nat Rev Neurosci. 2001; 2: 119-28. [E fetotsoe]
[34] Tšepo BT, Nye HE, Kelz MB, Self DW, Iadarola MJ, Nakabeppu Y, et al. Tlhahiso ea motsoako oa AP-1 oa nako e telele o qapiloeng ke liprotheine tse kang Fos ka bokong ka cocaine e sa feleng le kalafo tse ling tse sa foleng. Neuron. 1994; 13: 1235-44. [E fetotsoe]
[35] Colby CR, Whisler K, Steffen C, Nestler EJ, Self DW. Striatal cell Type overexpression e khethehileng ea DeltaFosB e ntlafatsa ts'usumetso ea koae. J Neurosci. 2003; 23: 2488-93. [E fetotsoe]
[36] Ehrlich ME, Sommer J, Canas E, Unterwald EM. Litoeba tsa Periadolescent li bonts'a ntlafatso ea ntlafatso ea DeltaFosB ho arabela cocaine le amphetamine. J Neurosci. 2002; 22: 9155-9. [E fetotsoe]
[37] Pascual MM, Moruti V, Bernabeu RO. Khetho ea sebaka sa Nikotine e ile ea etsa hore ho be le phosphorylation ea CREB le polelo ea Fos bokong ba rat ea batho ba baholo. Psychopharmacology (Berl) 2009; 207: 57-71. [E fetotsoe]
[38] Philpot RM, Engberg ME, Wecker L. Liphello tsa ho pepesetsoa ha nicotine ka ts'ebetso ea locomotor le maemo a pCREB maemong a makatsang a litoeba tsa bocha. Behav Brain Res 2012; 230: 62-8. [E fetotsoe]
[39] Raiff BR, Dallery J. Liphello tsa nicotine e mpe le e sa foleng ho likarabo tse bolokiloeng ke li-supplement tsa mantlha le tse maemong. Clin Psychopharmacol. 2006; 14: 296-305. [E fetotsoe]
[40] Raiff BR, Dallery J. Ho ata ha nicotine e le setsi se matlafatsang lipakeng: litlamorao tsa ho araba tse bolokiloeng ke li-supplement tsa mantlha le tse boemo le ho hanela ho timela. Psychopharmacology (Berl) 2008; 201: 305-14. [E fetotsoe]
[41] Popke EJ, Mayorga AJ, Fogle CM, Paule MG. Litlamorao tsa nicotine e hlobaetsang mabapi le boits'oaro bo sebetsang ho likhoto. Pharmacol Biochem Behav. 2000; 65: 247-54. [E fetotsoe]
[42] Philpot RM, Badanich KA, Kirstein CL. Boemo ba sebaka: Liphetoho tse amanang le lilemo tsofatsong e thabisang le e nyenyefatsang ea joala. Mofuta Oa Kliniki 2003; 27: 593-9. [E fetotsoe]
[43] Philpot R, Kirstein C. Liphapang tse bang teng karabong ea dopaminergic e tlisoang ke ho pepesoa hoa ethanol khafetsa. Ann NY Acad Sci. 2004; 1021: 422-6. [E fetotsoe]
[44] Philpot RM, Wecker L, Kirstein CL. Ho pepesetsoa hoa ethanol khafetsa nakong ea bocha ho fetola maemo a nts'etsopele a tlhahiso ea dopaminergic ho tsoa kholumong e bokellanang. Int J Dev Neurosci. 2009; 27: 805-15. [E fetotsoe]
[45] Sato SM, Wissman AM, McCollum AF, Woolley CS. Palo e lekanyelitsoeng ea polelo ea "cocaine-ikiwa" DeltaFosB e tsamaeang le likhoto tsa banna le basali. PloS One. 2011; 6: e21783. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
[46] Asin KE, Wirtshafter D, Tabakoff B. Ho hloleha ho theha sebaka se ratoang ke li-ethanol ka likhoto. Pharmacol Biochem Behav. 1985; 22: 169-73. [E fetotsoe]
[47] Huston JP, Silva MA, Sehlooho B, Muller CP. Ke maemo afe a khethiloeng sebakeng se khethiloeng? Mekhoa ea Pharmacol Sci. 2013; 34: 162-6. [E fetotsoe]
[48] Smith AM, Kelly RB, Chen WJ. Ho pepesetsoa ha nicotine ho sa feleng nakong ea periadolescence ha ho eke ho kenella ha ethanol nakong ea ho ba motho e moholo lilemong tsa likhoto. Mofuta Oa Kliniki 2002; 26: 976-9. [E fetotsoe]
[49] Adriani W, Laviola G. Windows ea kotsing ea ho ba le ts'ebetso ea kelello le leano la ho phekola lilemong tsa bocha tsa methapo ea methapo. Behav Pharmacol. 2004; 15: 341-52. [E fetotsoe]
[50] Chambers RA, Taylor JR, Potenza MN. Litla-morao tsa nts'etsopele ea kholo ea bongoana: nako e thata ea ho lemalla tlhekefetso. Ke J Psychiatry. 2003; 160: 1041-52. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
[51] Crews F, He J, Hodge C. Ho nts'etsopele ea bongoaneng: nako e thata ea ho lemalla ho lemalla. Pharmacol Biochem Behav. 2007; 86: 189-99. [E fetotsoe]
[52] Quinn PD, Harden KP. Liphetoho tse fapaneng phapusing ea ho batla ho kenella le ho ts'oaroa ha maikutlo le ho nyoloha ha ts'ebeliso ea lithethefatsi ho tloha bocheng ho ea ho motho e moholo. Dev Psychopathol. 2012: 1-17. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
[53] Soderstrom K, Qin W, Williams H, Taylor DA, McMillen BA. Nikotine e eketsa polelo ea FosB kahara likarolo tsa boko tse amanang le moputso nakong ea bocha le ea bongoana. Psychopharmacology (Berl) 2007; 191: 891-7. [E fetotsoe]
[54] Tzschentke TM. Ho lekanya moputso ka paradigm e khethiloeng ke sebaka: tlhahlobo e felletseng ea litlamorao tsa lithethefatsi, tsoelo-pele ea morao-rao le litaba tse ncha. Prog Neurobiol. 1998; 56: 613-72. [E fetotsoe]
[55] Tzschentke TM. Ho lekanya moputso ka paradigm ea boemo bo ikhethileng: ntlafatso ea lilemo tse leshome tse fetileng. Adict Biol. 2007; 12: 227-462. [E fetotsoe]
[56] Ohnishi YN, Ohnishi YH, Hokama M, Nomaru H, Yamazaki K, Tominaga Y, et al. FosB e bohlokoa molemong oa ntlafatso ea khatello ea maikutlo le ho hanyetsa maikutlo a locomotor ke DeltaFosB. Psychology ea Biol. 2011; 70: 487-95. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
[57] Vialou V, Robison AJ, Laplant QC, Covington HE, 3rd, Dietz DM, Ohnishi YN, et al. DeltaFosB ho li-circuits tsa moputso oa boko li thusa ho sebetsana le khatello ea maikutlo le likarabo tse khahlanong le khatello ea maikutlo. Nat Neurosci. 2010; 13: 745-52. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
[58] Christianen AM, Dekloet AD, Ulrich-Lai YM, Herman JP. "Snacking" e baka karabelo ea nako e telele ea likarabo tsa khatello ea kelello ea HPA le ntlafatso ea polelo ea bokhabane ea FosB / deltaFosB likhethong. Physiol Behav. 2011; 103: 111-6. [Tlhahiso ea mahala ea PMC] [E fetotsoe]