Pavlovian inhibitory conditioning and tolerance to pentobarbital-induced hypothermia in rats

In this experiment we investigated inhibitory Pavlovian conditioning in the development of tolerance to pentobarbital-induced hypothermia. During an initial phase, one group of rats (discrimination group) received training in which, on alternate days, one conditional stimulus (CS+) was associated with administration of 30 mg/kg pentobarbital, and a different conditional stimulus (CS-) was associated with administration of physiological saline. During the phase, control groups received either exposure to both CSs but not the drug or to the drug but no CSs or to neither the CSs nor the drug. Subsequently, half the rats in each group received injections of pentobarbital in the presence of one of the CSs and the remaining half in the presence of the other CS. Rats from the discrimination group injected with pentobarbital in the presence of CS+ displayed the most tolerance (i.e., smallest drug effect), whereas rats from the discrimination group injected with pentobarbital in the presence of CS- displayed the least tolerance (i.e., greatest drug effect). The attenuation of tolerance seen in rats of the discrimination group injected in the presence of CS- provides evidence of inhibitory Pavlovian conditioning. Additional evidence of inhibitory conditioning was provided by the fact that CS2 enhanced the hypothermic effects of pentobarbital in the discrimination group, whereas CS1 attenuated these effects. Implications of the results for the nature of inhibitory conditioning are discussed.