Discriminative stimulus properties of cocaine in the rat using a two-choice discrete-trial avoidance paradigm

Abstract

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)methoxy]ethyl]-4-(3-phenylpropyl)piperazine 2HCl (GBR 12909) (30.0 mg/kg), methamphetamine (0.3 mg/kg), apomorphine (0.3 mg/kg), and the D 2 dopamine agonist quinpirole (0.1 mg/kg), but not to the D 1 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 D 1 dopamine antagonist 7-chloro-2,3,4,5-tetrahydro-3-methyl- phenyl-1- H-benzazepine-7- ol maleate (SCH23390) (0.01–0.03mg/kg), and the D 2 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 D 1 and D 2 dopamine receptors contribute to the discriminative stimulus effects of cocaine.