Dopamine D3 receptor modulation of dopamine efflux in the rat nucleus accumbens.
The effect of antipsychotics on electrically evoked dopamine efflux in the rat nucleus accumbens core and shell was investigated, using in vitro fast cyclic voltammetry. In the nucleus accumbens core, the dopamine D2/D3 receptor agonist, (+/-)7-OH-DPAT ((+/-)-2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphthalene), inhibited dopamine efflux with a pEC50 of 8.1. Clozapine, haloperidol, sulpiride and the selective dopamine D3 receptor antagonist, SB-277011-A, had no effect on dopamine efflux per se but all attenuated the (+/-)7-OH-DPAT-induced-inhibition of dopamine efflux, with pA2 values of 6.6, 7.9, 7.0 and 7.6, respectively. In the nucleus accumbens shell, (+/-)7-OH-DPAT inhibited dopamine efflux with a pEC50 of 8.3. Clozapine and SB-277011-A had no effect on dopamine efflux. In contrast, haloperidol and sulpiride significantly increased dopamine efflux through a D2 receptor-mediated mechanism. Clozapine, haloperidol, sulpiride and SB-277011-A attenuated the (+/-)7-OH-DPAT-induced inhibition with pA2 values of 7.3, 8.6, 7.6 and 8.2, respectively. These data demonstrate that dopamine efflux is modulated by both dopamine D2 and D3 receptors in the rat nucleus accumbens.
Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK. Claire_2_Roberts@gsk.com
Claire
C
Roberts
Robert
R
Cummins
Zaira
Z
Gnoffo
James N C
JN
Kew
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D050637:Receptors, Dopamine D3 / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology; D044005:Tetrahydroisoquinolines / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C493595:Drd3 protein, rat; D009570:Nitriles; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C409982:SB 277011; D044005:Tetrahydroisoquinolines; D013764:Tetrahydronaphthalenes; D013469:Sulpiride; D003024:Clozapine; D006220:Haloperidol; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine