The contribution of environmental cues to cross-tolerance between ethanol and pentobarbital.
The contribution of Pavlovian conditioning of environmental cues has been studied in relation to tolerance to ethanol-induced hypothermia and cross-tolerance to pentobarbital. Two groups of 12 male Sprague-Dawley rats were exposed every other day to a distinctive set of environmental cues paired with an IP injection of either ethanol 2.5 g/kg or an equivalent volume of isotonic saline. On alternating non-drug days, both groups received saline in the animal room. When they were tested for tolerance to the hypothermic effect of ethanol 2.5 g/kg and cross-tolerance to pentobarbital 25 mg/kg in each environment, tolerance and cross-tolerance in the ethanol-treated group were significantly more pronounced in the ethanol-paired environment than in the saline-paired environment. This indicates the importance of a conditional factor in tolerance and cross-tolerance in this paradigm. Determination of blood levels of ethanol and pentobarbital at various times after injection indicated that conditioned tolerance and cross-tolerance can be explained in part by dispositional factors.
el-Ghundi
M
M
Department of Pharmacology, University of Toronto, Ontario, Canada.
Kalant
H
H
Lê
A D
AD
Khanna
J M
JM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D003463:Cues; D004361:Drug Tolerance; D004777:Environment; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects; D008297:Male; D010424:Pentobarbital / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000431:Ethanol; D010424:Pentobarbital