The discriminative stimulus properties of self-administered ethanol are mediated by GABA(A) and NMDA receptors in rats

Rationale: The neurobiological systems that mediate the discriminative stim ulus effects of self-administered drugs are largely unknown. The present st udy examined the discriminative stimulus effects of self-administered ethan ol. Methods: Rats were trained to discriminate ethanol (1 g/kg, IF) from sa line on a two-lever drug discrimination task with sucrose (10% w/v) reinfor cement. Test sessions were conducted with ethanol (0 or 10% v/v) added to t he sucrose reinforcement to determine if self-administered ethanol would in teract with the discriminative stimulus effects of investigator-administere d ethanol, or with the ethanol-like discriminative stimulus effects of the GABA(A)-positive modulator pen tobarbital or the non-competitive NMDA antag onist MK-801. Results. During a saline test session, ethanol (10% v/v) was added to the sucrose reinforcement. Responding by all animals began accurat ely on the saline-appropriate lever and then switched to the ethanol-approp riate lever after rats self-administered a mean dose of 1.2 +/- 0.14 g/kg e thanol. During cumulative self-administration trials, responding initially occurred on the saline lever and then switched to the ethanol-appropriate l ever after ethanol (0.68 +/- 0.13 g/kg) was self-administered. Investigator -administered MK-801 (0.01-1.0 mg/kg, cumulative IF) and pentobarbital (0.3 -10.0 mg/kg, cumulative IF) dose-dependently substituted for ethanol. When ethanol (10% v/v) was added to the sucrose reinforcer, MK-801 and pentobarb ital dose-response curves were shifted significantly to the left. Conclusio ns: Self-administered ethanol substituted for and potentiated the stimulus effects of investigator-administered ethanol, suggesting that the discrimin ative stimulus effects of self-administered ethanol are similar to those pr oduced by investigator-administered ethanol. Self-administered ethanol enha nced the ethanol-like discriminative stimulus effects of MK-801 and pentoba rbital, which suggests that the discriminative stimulus effects of self-adm inistered ethanol are mediated by NMDA and GABA(A) receptors.