The discriminative stimulus properties of self-administered ethanol are mediated by GABA(A) and NMDA receptors in rats.
BACKGROUND
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.
Hodge
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CW
Department of Neurology, Ernest Gallo Clinic and Research Center, University of California at San Francisco, 94608, USA. chodge@itsa.ucsf.edu
Cox
A A
AA
Bratt
A M
AM
Camarini
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R
Iller
K
K
Kelley
S P
SP
Mehmert
K K
KK
Nannini
M A
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Olive
M F
MF
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004193:Discrimination Learning; D004192:Discrimination, Psychological / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012646:Self Administration
D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D016291:Dizocilpine Maleate; D010424:Pentobarbital