The discriminative stimulus properties of self-administered ethanol are mediated by GABAA and NMDA receptors in rats

• Published in: Psychopharmacologia Vol. 154; no. 1; pp. 13 - 22
• Main Authors: HODGE, Clyde W, COX, Amy A, BRATT, Alison M, CAMARINI, Rosana, ILLER, Kimberly, KELLEY, Stephen P, MEHMERT, Kristin K, NANNINI, Michelle A, OLIVE, M. Foster
• Format: Journal Article
• Language: English
• Published: Berlin Springer 22.02.2001
• Subjects: Alcoholism and acute alcohol poisoning; Behavioral psychophysiology; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Medical sciences; Miscellaneous; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Toxicology; Consumption; Intraperitoneal administration; Ethanol; Rat; Toxicity; Alcoholism; Rodentia; Instrumental conditioning; Glutamate receptor; Self administration; Learning; Alcoholic beverage; Vertebrata; Mammalia; Acquisition process; Substitution; Animal; Antagonist; Mechanism of action; NMDA receptor; Stimulus discrimination; Gabaergic receptor A; Chemical stimulus
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130000619

Rationale: The neurobiological systems that mediate the discriminative stimulus effects of self-administered drugs are largely unknown. The present study examined the discriminative stimulus effects of self-administered ethanol. Methods: Rats were trained to discriminate ethanol (1 g/kg, IP) from saline on a two-lever drug discrimination task with sucrose (10% w/v) reinforcement. Test sessions were conducted with ethanol (0 or 10% v/v) added to the sucrose reinforcement to determine if self-administered ethanol would interact with the discriminative stimulus effects of investigator-administered ethanol, or with the ethanol-like discriminative stimulus effects of the GABAA-positive modulator pentobarbital or the non-competitive NMDA antagonist MK-801. Results: During a saline test session, ethanol (10% v/v) was added to the sucrose reinforcement. Responding by all animals began accurately on the saline-appropriate lever and then switched to the ethanol-appropriate lever after rats self-administered a mean dose of 1. 2+0. 14 g/kg ethanol. During cumulative self-administration trials, responding initially occurred on the saline lever and then switched to the ethanol-appropriate lever after ethanol (0. 68+0. 13 g/kg) was self-administered. Investigator-administered MK-801 (0. 01-1. 0 mg/kg, cumulative IP) and pentobarbital (0. 3-10. 0 mg/kg, cumulative IP) dose-dependently substituted for ethanol. When ethanol (10% v/v) was added to the sucrose reinforcer, MK-801 and pentobarbital dose-response curves were shifted significantly to the left. Conclusions: Self-administered ethanol substituted for and potentiated the stimulus effects of investigator-administered ethanol, suggesting that the discriminative stimulus effects of self-administered ethanol are similar to those produced by investigator-administered ethanol. Self-administered ethanol enhanced the ethanol-like discriminative stimulus effects of MK-801 and pentobarbital, which suggests that the discriminative stimulus effects of self-administered ethanol are mediated by NMDA and GABAA receptors.