Effect of dopamine D2/D3 receptor antagonist sulpiride on amphetamine-induced changes in striatal extracellular dopamine.
Amphetamine increases extracellular dopamine and induces locomotor and stereotypical behaviors in rats. This study examined the effect of the dopamine D2/D3 receptor antagonist sulpiride (50 mg/kg s.c.) on the dopaminergic response to amphetamine (0.5, 2.0, or 8.0 mg/kg i.p.) in male Sprague-Dawley rats. Extracellular dopamine in the striatum was monitored using in vivo microdialysis and high performance liquid chromatography with electrochemical detection. Dopamine concentration curves were analyzed using non-linear regression and residual F-testing. Amphetamine enhanced extracellular dopamine in a dose-dependent manner. Sulpiride augmented the increase in dopamine induced by 0.5 and 2 mg/kg amphetamine by decreasing the rate of dopamine concentration fall off in the extracellular space (P<0.05). Sulpiride also potentiated the amount of dopamine increased by 8 mg/kg amphetamine, but did so by affecting the maximum concentration achieved (P<0.05), not the onset or offset rates. We conclude that the primary effect of a dopamine D2/D3 receptor antagonist is a potentiation of the effect of amphetamine on extracellular striatal dopamine levels, which may contribute to the enhanced stereotypic effects observed when paired with amphetamine.
Jaworski
J N
JN
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Austin 78712, USA.
Gonzales
R A
RA
Randall
P K
PK
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D050637:Receptors, Dopamine D3; D013469:Sulpiride / Q000494:pharmacology*; D013997:Time Factors
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D050637:Receptors, Dopamine D3; D013469:Sulpiride; D000661:Amphetamine; D004298:Dopamine