Interactions of ethanol with nicotine, dizocilpine, CGP 40116, and 1-(m-chlorophenyl)-biguanide in rats.
The present study examined the effect of ethanol (0.25-1.0 g/kg, I.P.) alone and in combination with drugs affecting different ligand-gated ion channels on a horizontal locomotor activity of male Wistar rats. None of the drugs given alone affected the locomotor activity. Similarly, combining ethanol either with nicotine (0.1 or 0.6 mg/kg, S.C.) or the competitive NMDA receptor antagonist, CGP 40116 (0.5 mg/kg, I.P.) did not result in any significant changes in ambulation. On the other hand, a significant hyperadditive interaction between ethanol (0.5 or 1.0 g/kg) and the uncompetitive NMDA receptor antagonist, dizocilpine (0.1 mg/kg, I.P.) was found. Thus, a combined administration of ethanol and dizocilpine produced a marked stimulation of the locomotor activity. Combining 1.0 g/kg ethanol with the 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide (5.0 mg/kg, I.P.) tended to produce locomotor stimulation. Our results suggest the existence of interaction between ethanol and the NMDA receptor complex in mediation of locomotor stimulation. Alternatively, a common neurotransmitter system (other than glutamatergic) mediate central stimulatory effects of ethanol and dizocilpine. A possible role of dopamine in this interaction is being discussed.
Bienkowski
P
P
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.
Koros
E
E
Piasecki
J
J
Kostowski
W
W
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001645:Biguanides / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D001645:Biguanides; D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D018722:Nicotinic Agonists; D016194:Receptors, N-Methyl-D-Aspartate; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D000431:Ethanol; D016291:Dizocilpine Maleate; D009538:Nicotine; D015763:2-Amino-5-phosphonovalerate; C065734:1-(3-chlorophenyl)biguanide