Effect of altering dopamine or serotonin neurotransmitters upon cathinone discrimination.
Rats were trained to discriminate between the stimulus properties of 0.8 mg/kg l-cathinone 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 cathinone doses. An analysis of the dose-response curve indicated an ED50 value of 0.23 mg/kg. Pretreatment with CGS 10746B (5-20 mg/kg) resulted in a dose-related decrease in cathinone discrimination with the highest dose blocking cathinone discrimination. In contrast to the ability of this dopamine release inhibitor to decrease cathinone discrimination, pretreatment with three doses of the calcium channel blocker isradipine (2.5-10 mg/kg) or with the 5-HT3 antagonist MDL 72222 (0.1-0.4 mg/kg) had no effect upon cathinone discrimination. The results suggest that cathinone controls differential responding in a discriminative stimulus task by a mechanism involving presynaptic release of dopamine, which may not be regulated by either neuronal calcium influx through L-type calcium channels or by serotonergic neurons.
Schechter
M D
MD
Department of Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown 44272-0095.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D017275:Isradipine; D008297:Male; D018377:Neurotransmitter Agents / Q000502:physiology*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013841:Thiazepines / Q000494:pharmacology; D014326:Tropanes / Q000494:pharmacology
D000470:Alkaloids; D014150:Antipsychotic Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D018377:Neurotransmitter Agents; D011619:Psychotropic Drugs; D012702:Serotonin Antagonists; D013841:Thiazepines; D014326:Tropanes; D012701:Serotonin; C023665:cathinone; C049819:CGS 10746B; C042253:bemesetron; D004298:Dopamine; D017275:Isradipine