Effects of self- and experimenter-administered cocaine on subsequent ethanol drinking in rhesus monkeys.

BACKGROUND: One possible reason for the lack of FDA-approved pharmacotherapies to treat cocaine use disorder (CUD) is that, although cocaine is typically used in combination with alcohol, it is studied in isolation in preclinical studies. A better understanding of the cocaine-alcohol interactions that promote polysubstance use (PSU) will improve animal models of CUD and hasten pharmacotherapy development. We used a rhesus monkey model of cocaine-alcohol PSU to investigate one possible mechanism: that alcohol is used to mitigate negative effects associated with termination of cocaine use. METHODS: In 6 adult male rhesus monkeys, the relationship between self-administered cocaine intake and oral ethanol intake 2hours later was examined during self-administration of cocaine (0.0003-0.3mg/kg per injection, i.v.) under a fixed-ratio 30 schedule (FR30) or a progressive-ratio (PR) schedule. Next, ethanol consumption was measured 0-120minutes after experimenter-administered cocaine (0.3-1.7mg/kg, i.v.). RESULTS: Self-administered cocaine intake under both FR30 and PR schedules was unrelated to oral ethanol intakes 2hours later. When cocaine was administered non-contingently, cocaine decreased ethanol intake as well as intake of a non-alcoholic solution in monkeys who never consumed ethanol (n=4) in a time- and dose-dependent manner. CONCLUSIONS: Taken together, the results do not provide evidence for cocaine-induced increases in ethanol consumption. By extension, the results do not support the hypothesis that cocaine users drink alcohol to counteract negative effects that occur after terminating use. This finding implies either that such effects do not exist or that such effects exist but are unaffected by ethanol.

Discriminative stimulus properties of two training doses of gabapentin in rats: Substitution by pregabalin, diazepam, and pentobarbital.

Gabapentin is used for the treatment of many conditions, including seizures, pain, and anxiety. Increasing reports of nonprescribed use suggest that gabapentin may elicit positive subjective effects. The present study was conducted to examine the subjective effects of gabapentin using rats trained to discriminate either a 30.0 mg/kg or 300.0 mg/kg dose of gabapentin versus vehicle on a two-choice drug discrimination task. Both doses of gabapentin were established as discriminative stimuli, and the 300.0 mg/kg dose was more readily established compared to the 30.0 mg/kg dose. Full substitution (> 80% gabapentin-lever responding) occurred by the training drug and by the gabapentinoid compound pregabalin. Partial substitution (> 20% gabapentin-lever responding) was shown by the opioid compounds morphine and fentanyl, and dose combinations of the opioid receptor antagonist naltrexone with the gabapentin training doses reduced the percentage of gabapentin-lever responding to below 80%. Partial substitution for both training doses of gabapentin occurred with the cannabinoid Δ9-tetrahydrocannabinol. The barbiturate compound pentobarbital and the benzodiazepine compound diazepam were only tested for substitution for the 300.0 mg/kg dose of gabapentin and these compounds produced full substitution. These findings demonstrate that gabapentin establishes a robust discriminative cue and exhibits stimulus effects closely similar to pregabalin, pentobarbital, and diazepam. Since pregabalin, pentobarbital, and diazepam carry a risk of problematic use and are classified as controlled substances, further evaluations of gabapentin's risks in this regard are warranted. (PsycInfo Database Record (c) 2024 APA, all rights reserved).