mGluR5 ts'ebetso ea nucleus accumbens ha hoa hlokahala bakeng sa boitšoaro bo bobe ba ho kopanela liphate kapa ho fokotsa tšoaetso ea li-amphetamine likarabo tsa thobalano (2016)

Neuropharmacology. 2016 Aug; 107: 122-30. Doi: 10.1016 / j.neuropharm.2016.03.002

Pitchers KK1, Di Sebastiano AR2, Coolen LM3.

inahaneloang

Meputso ea tlhaho le li-psychostimulants li baka polasetiki e tšoanang ea neural ho li-nucleus accumbens (NAc). Ntle le moo, boiphihlelo ba thobalano ho likhoto tsa banna bo baka ts'ebetso e eketsehang ea locomotor le khetho ea sebaka se hlophisitsoeng (CPP) e hlohlellelitsoeng ke d-Amphetamine (amph). Ea morao-rao e ipapisitse le nako ea ho ithiba moputsong oa thobalano. Thutong ena, karolo ea ts'ebetso ea mGluR5 ho NAc bakeng sa polelo ea ho nyalana le litlamorao tse matlafatsang tsa boiphihlelo ba thobalano e ile ea lekoa. Taba ea mantlha, li-intra-NAc infusions tsa bahanyetsi ba mGluR5 MPEP (1 kapa 10 μg / μL) kapa MTEP (1 μg / μL) 15 min pele ho ho nyalana nakong ea linako tsa 4 tsa letsatsi le letsatsi li ne li se na tšusumetso ho boits'oaro ba banna ba thobalano. Kamora moo, banna bana ba nang le boiphihlelo ba ho etsa thobalano ba ile ba lekoa bakeng sa ts'ebetso ea li-amph-indocotor le CPP kamora beke e le 'ngoe ea ho ila moputso oa thobalano. Ntle le moo, ba batona ba nang le thobalano ba fumaneng MPEP, MTEP kapa infusions tsa koloi pele ho linako tse 4 tsa ts'ebetso ea letsatsi le letsatsi li kenyelelitsoe. Ho hlohlelletsa sefapano sa ho hlohlona kapa CPP ha hoa ka ha thibeloa ke lehloeo la NAc mGluR5 nakong ea ho fumana boiphihlelo ba thobalano. Sebakeng seo, liphoofolo tse nang le botona le botšehali tse amohetseng bahanyetsi ba NAc mGluR5 ntle le ho nyalana li bonts'itse likarabo tsa maiketsetso tse matlafalitsoeng ke amph le CPP e ntlafalitsoeng joalo ka banna ba nang le boiphihlelo ba thobalano. Kamora nako, re bonts'itse hore boiphihlelo ba thobalano bo bakile taolo e telele ea tlase ea protheine ea mGluR5 ho NAc, ho latela boits'oaro ba thobalano. Hammoho, liphuputso tsena li fana ka maikutlo a hore ts'ebetso ea mGluR5 ho NAc ha e bohlokoa molemong oa polelo, empa phokotso e bakiloeng ke boiphihlelo ba protheine ea mGluR5 e ka kenya letsoho ho matlafatseng likarabo tsa amph ka boiphihlelo ba thobalano le boits'oaro.

LINKOTSO: Amphetamine; Tsebiso ea boitšoaro Sebaka se khethiloeng sa sebaka; Glutamate; Moputso; protheine ea mGluR

PMID: 26946431

DOI: 10.1016 / j.neuropharm.2016.03.002


 

TŠOHLOA

Lithethefatsi tsa tlhekefetso le meputso ea tlhaho, ho kenyelletsa boitšoaro ba botona ba banna, li bontšitsoe hore li se ke tsa kenya tšebetsong libaka tse fetang tsa bokong (Balfour et al., 2004; Frohmader et al., 2010b) empa hape li sebelisa li-medioptericity tsa methapo e tšoanang le methapo ea methapo ho etsa hore neuroplasticity e be teng liphetoho tsa boitšoaro (Pitchers et al., 2010a, 2012, 2013, 2014, Beloate et al., 2016). Tsamaiso ea psychostimulant e baka keketseho e matla ea glutamate ea extracellular ho NAc (Del Arco et al., 1999; Grey et al., 1999; Reid and Berger, 1996), empa cocaine e phetoang hangata e baka phokotseho ea litheko tsa basal glutamate (Baker et al., 2003; Madayag et al., 2007; McFarland et al., 2003).

Li-glutamate kapa mGluR5 agonists li kenya tšebetsong mGluR5 le ho baka takatso e hlakileng le e potlakileng ea mGluR5 e kenyelletsang taolo ea mGluR5 (Dhami le Ferguson, 2006; Gereau le Heinemann, 1998). K'hok'heine e phetoang khafetsa le nako e atolositsoeng ea ho itima lijo (empa eseng kamora letsatsi la 1 feela) e baka ho fokotseha ha polelo ea mGluR5 ho striatum, mme ka lebaka leo, ho fokotsa sehlopha sa 1 mGluR-Mediated ho eketseha ha glutamate ea extracellular

Ho 'nile ha fanoa ka tlhahiso ea hore maemo a glutamate a theotsoeng a emela karabelo ea tefo ea ponaletso ea moputso e khutsitseng le hore mosebetsi o tlase oa mGluR5 o tla fumana litlamorao tsa tokollo ea glutamate e entsoeng ke lithethefatsi e ka hlahisang likarabo tse susumetsang tse susumetsang maikutlo (Kalivas et al., 2009). Ho bonahala ho na le ho tšoana pakeng tsa boiphihlelo ba thobalano le psychostimulants e pheta-phetoang e bakang ho fokotseha ka mokhoa o ka bang teng, ho fokotsa ho ipatileng hoa litekanyetso tsa mGluR5 ho NAc. Ho feta moo, ho fokotseha hona ha li-receptor tsa mGluR5 tse nang le boiphihlelo ba thobalano ho hokahane ka nakoana le likarabelo tse lemositsoeng ho li-psychostimulants le maikutlo a thobalano (Pitchers et al., 2010a, 2010b, 2012, 2013). Haholo-holo, litlamorao tsa boiphihlelo ba botona le botšehali ho sensitization ea amph-CPP le maemong a mGluR5 ka bobeli li ipapisitse le nako ea ho ila le ho phehella ka ho khaotsa ho sa feleng (Pitchers et al., 2010a).

Ho fapana le seo, litlamorao tsa boiphihlelo ba botona le botšehali ho sensomization ea locomotor ha lia itšetleha ka nako ea thobalano mme li bonoa ka letsatsi le le leng kamora boiphihlelo ba thobalano. Ka hona, ho fokotsoa ha protheine ea mGluR5 ho ka kenya letsoho ho etseng phepelo ea maikutlo a thobalano a khothalletsoang ka thobalano, empa ha ho bonahale e le lebaka la pele la mabaka. Lithuto tsa nako e tlang li hlokahala ho etsa lipatlisiso tse ling tsa bohlokoa ba taolo e tlase ea polelo ea mGluR5 kamora boiphihlelo ba thobalano holima tšebetso ea li-receptor le maemo a glutamate.

Morero oa glutamatergic o tsoang ho mPFC ho ea ho NAc, le mGluR5 li kentsoe tšebetsong ea ho khutlisetsoa hoa lithethefatsi le ho fella ka ho ithuta Ghasemzadeh et al., 2009; Kalivas et al., 2005; Knackstedt et al., 2014). mGluR5 e bontšitsoe e le ea bohlokoa bakeng sa likarabo tsa cocainerelated ka ts'ebeliso ea litoeba tsa mGluR5 KO. mGluR5 KO litoeba ha li tsamaise koae, hape ha li bonts'e liphetoho tse khothalletsoang ke koae mosebetsing oa locomotor (Chiamulera et al., 2001). Tsamaiso ea systemic ea mGluR5 antagonist MPEP e fokotsa cocaine, morphine le nicotine self tsamaiso le boitšoaro bo latelang ba batlang lithethefatsi (Aoki et al., 2004; Chiamulera et al., 2001; Kumaresan et al., 2009; Popik le Wrobel, 2002; Tessari et al., 2004). Ho feta moo, ka ho susumetsa mGluR5 ho NAc, ho khutlisetsoa ka matla ho cue ho ka khonehang

Ka lehlakoreng le leng, MPEP ha e ame nts'etsopele kapa polelo ea lijo tsa CPP (Herzig et al., 2005). Mona, ha rea ​​ka ra leka antagonism ea mGluR5 ka nako ea ho bua ka ts'ebetso ea sensorised amph-indued locomotor kapa moputso oa amph. Boithuto ba hona joale bo bonts'a hore ho hanyetsa ka nako ea mGluR5 nakong ea boiphihlelo ba thobalano ha hoa ka ha thibela litlamorao tsa boiphihlelo ba botona le botšehali ho likarabo tsa amph. Ho qhekella mosebetsi oa li-receptor ka nako ea liteko tsa amph, ho fapana le nakong ea nts'etsopele, ho ka tšoana hantle le liteko tse ngata tsa lithethefatsi tsa tlhekefetso mme li ka bonts'a phello ho liphoofolo tse nang le thobalano.

Ka kakaretso, sephetho sa rona se fana ka maikutlo a hore ts'ebetso ea antagonism ea mGluR5 ts'ebetsong ea NAc ha e nyenyefatse boitšoaro ba thobalano ebile ha e thibele litlamorao tsa nako e telele tsa boiphihlelo ba thobalano le ho ila boitšoaro. Leha ho le joalo, Tsamaiso ea mohanyetsi oa mGluR5 o le mong ntle le boitšoaro ba thobalano e baka ts'ebetso ea sensor ea amph-induction e ntlafalitsoeng le moputso o ntlafalitsoeng oa amph, o etsisa litlamorao tsa boiphihlelo ba thobalano. Kamora moo, ho ile ha bonts'oa hore boiphihlelo ba thobalano bo lateloang ke ho ila thobalano nako e telele ho tsoa ho moputso oa thobalano bo bakile taolo e tlase ea liprotheine tsa mGluR5 ho NAc, tseo ka lehlakoreng le leng li ka bakang litlamorao tse matla tsa boiphihlelo ba thobalano le bootsoa.