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.
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.
Authors: Clyde W Hodge; Michael F Miles; Amanda C Sharko; Rebekah A Stevenson; Jennie R Hillmann; Veronique Lepoutre; Joyce Besheer; Jason P Schroeder Journal: Psychopharmacology (Berl) Date: 2005-11-15 Impact factor: 4.530
Authors: Joyce Besheer; Kristen R Fisher; Reginald Cannady; Julie J M Grondin; Clyde W Hodge Journal: Behav Brain Res Date: 2011-12-23 Impact factor: 3.332
Authors: Kimberly A Badanich; Tamara L Doremus-Fitzwater; Patrick J Mulholland; Patrick K Randall; Eric Delpire; Howard C Becker Journal: Genes Brain Behav Date: 2011-08-15 Impact factor: 3.449