title: Cocaine discrimination is attenuated by isradipine and CGS 10746B.
abstract: The discriminative stimulus properties of cocaine are thought to be mediated by dopaminergic mechanisms that may be modulated by calcium ion influx and/or interact with 5-hydroxytryptamine3 (5-HT3) receptors. To test these possibilities, rats were trained to discriminate between the stimulus properties of 10.0 mg/kg cocaine and its vehicle in a two-lever, food-motivated operant task. Once trained, rats showed a dose-related decrease in discriminative performance when tested with lower cocaine doses. An analysis of the dose-response curve indicated an ED50 value of 3.04 mg/kg. Pretreatment with the presynaptic dopamine release-inhibiting agent CGS 10746B (20-40 mg/kg) resulted in a dose-related decrease in cocaine discrimination with the highest dose significantly attenuating cocaine discrimination. Pretreatment with 10-30 mg/kg isradipine, a calcium channel blocker, also resulted in a dose-related decrease in cocaine discriminative performance. In contrast to these positive results, pretreatment with the 5-HT3 receptor antagonist MDL 72222 (3.5-7.0 mg/kg), or the same doses of ibogaine, did not significantly affect cocaine discrimination. The results suggest that cocaine controls differential responding in a discriminative stimulus task by mechanisms that involve presynaptic release of dopamine, which may be regulated by neuronal calcium influx through L-type calcium channels.
authors.affiliation: Department of Pharmacology, College of Medicine, Northeastern Ohio Universities, Rootstown 44272-0095.
authors.forename: M D
authors.initials: MD
authors.lastname: Schechter
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007050:Ibogaine / Q000494:pharmacology; D017275:Isradipine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology; D013841:Thiazepines / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D002121:Calcium Channel Blockers; D012702:Serotonin Antagonists; D013841:Thiazepines; D014326:Tropanes; D007050:Ibogaine; C049819:CGS 10746B; D003042:Cocaine; C042253:bemesetron; D017275:Isradipine