title: Activation of the A10 mesolimbic system by the sigma-receptor agonist (+)SKF 10,047 can be blocked by rimcazole, a novel putative antipsychotic.
abstract: This study evaluated with electrophysiological and behavioral techniques the ability of rimcazole, a novel putative antipsychotic and selective sigma-receptor ligand, to antagonize the stimulation of the mesocorticolimbic dopamine system by the sigma-agonist, (+)SKF 10,047. Rimcazole effectively blocked the (+)SKF 10,047-induced excitation of ventral tegmental dopamine neurons while having no effect on either spontaneous activity or apomorphine-elicited slowing of A10 firing. Rimcazole also antagonized the behavioral hyperactivity produced by (+)SKF 10,047, but not by d-amphetamine which is also mediated through the same mesolimbic dopamine pathway. These data provide further evidence that rimcazole's novel pharmacologic profile may involve a blockade of sigma-receptors on mesocorticolimbic dopamine neurons.
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008032:Limbic System / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects*; D017480:Receptors, sigma
chemical_list: D014150:Antipsychotic Agents; D002227:Carbazoles; D011954:Receptors, Dopamine; D011957:Receptors, Opioid; D017480:Receptors, sigma; C012134:SK&F 10047; C034931:rimcazole; D010620:Phenazocine