Contingent drug tolerance: differential tolerance to the anticonvulsant, hypothermic, and ataxic effects of ethanol.
The kindled-convulsion model of epilepsy was used to study contingent tolerance to ethanol's (1.5 g/kg; IP) anticonvulsant, hypothermic, and ataxic effects in adult male rats. In the present experiments, three groups of amygdala-kindled rats received a series of bidaily (one every 48 h) convulsive stimulations: one group received ethanol 1 h before each stimulation; one group received ethanol 1 h after each stimulation; and another group served as the saline control. Tolerance to ethanol's anticonvulsant effect (Experiments 1 and 2) was greatest in those rats that received ethanol before each convulsive stimulation; whereas, tolerance to ethanol's hypothermic (Experiments 1 and 2) and ataxic (Experiments 2) effects developed in both groups that received ethanol. These results were predicted on the basis of the drug-effect theory of drug tolerance: the theory that functional drug tolerance is an adaptation to the disruptive effects of drugs on concurrent patterns of neural activity, not to drug exposure per se.
Kim
C K
CK
Department of Anatomy, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Pinel
J P
JP
Dalal
S
S
Kippin
T E
TE
Kalynchuk
L E
LE
Payne
G J
GJ
D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001259:Ataxia / Q000139:chemically induced*; D001831:Body Temperature / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004361:Drug Tolerance; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D000431:Ethanol / Q000494:pharmacology*; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D051381:Rats
D000927:Anticonvulsants; D002492:Central Nervous System Depressants; D000431:Ethanol