Discriminative stimulus properties of ethanol in rats: studies on the role of nitric oxide.
The present study examined the role of the L-arginine-nitric oxide pathway in mediation of the ethanol interoceptive (discriminative) cue. Adult male Wistar rats (n = 16) were trained to discriminate ethanol (1 g/kg, 10% v/v) from saline under a fixed-ratio 10 (FR10) schedule of sweetened milk reinforcement. A nonselective nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 10-540 mg/kg) did not substitute for ethanol. Similarly, a relatively selective neuronal NOS inhibitor, 7-nitroindazole (7-NI; 10-80 mg/kg), did not mimic the ethanol cue. However, both L-NAME and 7-NI produced significant reduction in the rate of operant responding. A nitric oxide precursor, L-arginine (100-500 mg/kg) neither substituted for nor antagonize the ethanol stimulus. Taken together, these results suggest that the L-arginine-nitric oxide pathway is not involved in mediation of the discriminative stimulus effects of ethanol in the rat.
Koros
E
E
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.
Kostowski
W
W
Bienkowski
P
P
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003463:Cues; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D007191:Indazoles; D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; D000431:Ethanol; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester