Discriminative stimulus properties of cocaine in the rat using a two-choice discrete-trial avoidance paradigm.
The discriminative stimulus effects of cocaine were studied in rats trained to discriminate 10.0 mg/kg cocaine from vehicle in a shock avoidance paradigm. Rats used could discriminate 10.0 mg/kg cocaine from vehicle within an average of 20 sessions after the start of discrimination training. Cocaine produced dose-dependent stimulus effects at 1.0- to 10.0-mg/kg doses. Cocaine (10.0 mg/kg) generalized to the dopamine reuptake inhibitor 1-[2-[bis(4-fluorophenyl)methyoxy]ethyl]-4-(3-phenylpropyl)piperaz ine 2HCl (GBR 12909) (30.0 mg/kg), methamphetamine (0.3 mg/kg), apomorphine (0.3 mg/kg), and the D2 dopamine agonist quinpirole (0.1 mg/kg), but not to the D1 dopamine agonist SK&F38393 (3.0-30.0 mg/kg). 1-Phenyl-2,3,4,5-tetrahydro-[1H]-3-benzazepine-7,8-diol HCl (SK&F38393) (10.0 mg/kg) combined with several doses (1.0-10.0 mg/kg) of cocaine shifted the stimulus generalization curve for cocaine to the left. Haloperidol (0.1 and 0.3 mg/kg), the D1 dopamine antagonist 7-chloro-2,3,4,5-tetrahydro-3-methyl-phenyl-1-H-benzazepine-7-ol maleate (SCH23390) (0.01-0.3 mg/kg), and the D2 dopamine antagonist S(-)-sulpiride (20.0 and 40.0 mg/kg) only partially blocked the stimulus effects of cocaine. Haloperidol (0.3 mg/kg) combined with SCH23390 (0.03 mg/kg) completely blocked the stimulus effects of cocaine. In addition, haloperidol (0.3 mg/kg) blocked the stimulus effects of quinpirole (0.1 mg/kg), in common with cocaine. These data suggest that both D1 and D2 dopamine receptors contribute to the discriminative stimulus effects of cocaine.
Ukai
M
M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Mori
E
E
Kameyama
T
T
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D004192:Discrimination, Psychological / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D004873:Ergolines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D015259:Dopamine Agents; D004873:Ergolines; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; D019257:Quinpirole; D008694:Methamphetamine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; C043425:vanoxerine; D003042:Cocaine; D006220:Haloperidol; D001058:Apomorphine