Conditioning and extinction of tolerance to the hypothermic effect of ethanol in rats

The contribution of classical conditioning to tolerance to the hypothermic effect of ethanol was examined. During the tolerance acquisition phase, rats were exposed at 4-day intervals to a distinctive set of environmental cues paired with injections of ethanol (1.4 g/kg, ip). Interspersed between these drug trials were exposures to an alternate set of cues paired with injections of saline. In addition, three groups experienced different amounts of stimulation and activity during drug exposure in order to determine whether "behavioral augmentation" of tolerance would occur. In subsequent tests, the rats were tolerant only in the presence of cues previously paired with ethanol. Moreover, this environmentally specific tolerance was associated with a conditioned hyperthermic response to placebo (saline) injections in the drug environment. An extinction procedure designed to weaken tolerance mediated by classical conditioning was also found to be effective. Evidence for conditioned tolerance was weakest in animals experiencing low levels of activity during the initial drug exposure periods.