The dopamine D4 receptor antagonist L-745,870: effects in rats discriminating cocaine from saline.
The contribution of dopamine D4 receptors to the discriminative stimulus effects of cocaine was evaluated by testing the selective dopamine D4 receptor antagonist, L-745,870 (3-([4-(4-chlororphenyl) piperazin-1-yl] methyl)-1 H-pyrrolo[2,3-b] pyridine), alone and in combination with cocaine, in rats trained to discriminate cocaine (10 mg/kg) from saline. The antagonist (1-10 mg/kg) failed to engender cocaine-appropriate responding when injected alone, and failed to modify the cocaine dose-response curve when injected as a pre-treatment; however, it reduced response rates dose-dependently. Conversely, the dopamine 'D1-like' receptor antagonist, SCH 39166 ((-)-trans-6,7,7a,8,9, 13b-hexahydro-3-chloro-2hydroxy-N-methyl-5H-benzo[d]napth o-¿2,1-b¿azepine, produced surmountable antagonism. Results suggest that dopamine D4 receptors play a negligible role in cocaine's discriminative stimulus effects, and further support a critical involvement of dopamine D1-like receptors.
Costanza
R M
RM
School of Psychology, University of Birmingham, Edgbaston, UK.
Terry
P
P
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology; D050638:Receptors, Dopamine D4
C099630:3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine; D018492:Dopamine Antagonists; C493601:Drd4 protein, rat; D011725:Pyridines; D011758:Pyrroles; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D003042:Cocaine