Validating conditioned antisickness theory, the explanation for the aversion failure phenomenon and the basis of a clinical nondrug conditioning strategy for the alleviation of nausea and emesis

grantor: University of TorontoMany species learn an aversion to a novel taste if made sick within hours of consumption. Most drugs induce such conditioned taste aversions (CTAs) and are therefore supposed to produce nausea or sickness, but such drugs are variably effective at optimal doses. By traditional Pavlovian conditioning principles, it should be possible in theory to increase the effectiveness of a drug that induces a mild CTA by first pairing it with a more effective drug tied induces a strong CTA. In Pavlovian terminology, if a conditioned stimulus (CS) drug such as pentobarbital--known to induce weak CTAs--is paired with an unconditioned stimulus (US) drug such as lithium--known to induce strong CTAs--on several occasions, the CS drug should come to induce stronger CTAs in a subsequent procedure than would otherwise be expected. One possible account of this aversion failure (avfail) phenomenon hinges on selective association of an internal drug state CS with a hypothetical homeostatic or ' antisickness' aftereffect of sickness. According to conditioned antisickness (CAS) theory, drug states model naturally occurring sequences of internal states. The CS drug corresponds to naturally occurring internal signals, the US drug to naturally occurring aftereffects, and conditioning enables the animal to better regulate its internal environment by anticipating the US. Drug-drug conditioning provides a general model for the involvement of Pavlovian conditioning in homeostatic regulation. The drug-drug pairings methodology has made CAS theory difficult to valid because nonindependence of the two drug states invites a pharmacological drug interaction alternative to a conditioning interpretation. The joint presence of particular CS and US drugs in the experimental group but not in Pavlovian controls could produce unique pharmacological effects that somehow mimic avfail. In an indirect test of CAS theory, Lett (1992) paired drug or place cues with lithium and found that rats with an experimental or forward pairings history ate less food on test, consistent with a traditional conditioned sickness account rather than with CAS. But rats eat dirt or clay in response to sickness and adaptively eat small amounts of food when clay is not available: Paradoxically, perhaps rats with a forward pairings history ate less food than controls because they were less rather than more sick. (Abstract shortened by UMI.)Ph.D