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.
Department of Anatomy, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
C K
CK
Kim
J P
JP
Pinel
S
S
Dalal
T E
TE
Kippin
L E
LE
Kalynchuk
G J
GJ
Payne
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