cgp-37849 and 1-(3-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.

Topics: 2-Amino-5-phosphonovalerate; Animals; Biguanides; Diazepam; Discrimination Learning; Drug Interactions; Ethanol; GABA Modulators; Male; Nicotine; Nicotinic Agonists; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Reinforcement Schedule; Serotonin Receptor Agonists

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.

Topics: 2-Amino-5-phosphonovalerate; Animals; Behavior, Animal; Biguanides; Central Nervous System Depressants; Dizocilpine Maleate; Drug Interactions; Ethanol; Excitatory Amino Acid Antagonists; Male; Motor Activity; Nicotine; Nicotinic Agonists; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate