Discrimination of ethanol in rats: effects of nicotine, diazepam, CGP 40116, and 1-(m-chlorophenyl)-biguanide.
The drug discrimination paradigm was used to evaluate the role of certain ligand-gated ion channels in the discriminative stimulus properties of ethanol. Rats were trained to discriminate ethanol (1.0 g/kg) from saline vehicle under the FR10 schedule of sweetened milk reinforcement. The discrimination of lower ethanol doses was enhanced by either the GABA(A) receptor positive modulator, diazepam (0.5 mg/kg), or nicotinic acetylcholine receptor agonist, nicotine (0.3 mg/kg). Neither diazepam nor nicotine produced any effect on the rate of responding. Both the NMDA receptor competitive antagonist, CGP 40116 (0.5 mg/kg) and the 5-HT) receptor agonist, 1-(m-chlorophenyl)-biguanide (5.0 mg/kg) enhanced the cueing properties of lower ethanol doses, but these effects were associated with a significant reduction in the response rate. The ethanol-like stimulus effects produced by diazepam or CGP 40116 were not influenced by 0.3 mg/kg nicotine. In contrast, CGP 40116 moderately enhanced the ethanol-like stimulus effects of diazepam. The present results show that: 1) pretreatment with nicotine, diazepam, CGP 40116 or 1-(m-chlorophenyl)-biguanide enhance the ethanol discrimination; 2) neither the GABA(A) nor the NMDA receptor complex alone is critically involved in the nicotine-induced enhancement of the ethanol discrimination; 3) NMDA receptor competitive antagonist and GABAergic benzodiazepine derivative may produce moderate additive effects in rats trained to discriminate ethanol.
Bienkowski
P
P
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.
Kostowski
W
W
D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001645:Biguanides / Q000008:administration & dosage / Q000494:pharmacology*; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012055:Reinforcement Schedule; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology
D001645:Biguanides; D018757:GABA Modulators; D018722:Nicotinic Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D017366:Serotonin Receptor Agonists; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D000431:Ethanol; D009538:Nicotine; D015763:2-Amino-5-phosphonovalerate; C065734:1-(3-chlorophenyl)biguanide; D003975:Diazepam