Differential effects of a dihydropyridine calcium channel antagonist on the components of ethanol tolerance.
The dihydropyridine calcium channel antagonist, nimodipine, was found to decrease the extent of tolerance that developed to the ataxic action of ethanol in experimental designs in which the tolerance was not context-specific, when ethanol was given by liquid diet. When ethanol was given by injection, so that cues were present for the effects of ethanol during the chronic treatment, tolerance to the ataxic actions of ethanol was unaffected. Nimodipine, however, decreased the tolerance to the hypothermic actions of ethanol, when the ethanol was given by injection. When the rats were given practice sessions on the motor task while under the influence of the ethanol, during the chronic treatment, nimodipine did not affect tolerance to the ataxic actions of ethanol. When nimodipine was given before the motor task learning and ethanol after the practice sessions, the tolerance to the ataxic effect of ethanol was increased. A similar schedule of drug treatment with the NMDA antagonist CGP37849 given before the practice sessions, and ethanol afterwards, resulted in decreased tolerance to ethanol. It is suggested that these changes in ethanol tolerance may be explained by dual actions of nimodipine in, firstly, decreasing the form of tolerance to ethanol that is not dependent on contextual cues and, secondarily, in increasing the learning of a motor task.
Smith
J W
JW
Drug Dependence Unit, Department of Psychology, Science Laboratories, South Road, Durham, UK.
Little
H J
HJ
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D020268:Alcohol-Induced Disorders, Nervous System / Q000188:drug therapy* / Q000503:physiopathology*; D000437:Alcoholism / Q000188:drug therapy* / Q000503:physiopathology*; D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007035:Hypothermia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology*; D011214:Practice, Psychological; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D002121:Calcium Channel Blockers; D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D000431:Ethanol; D009553:Nimodipine; D015763:2-Amino-5-phosphonovalerate