Several theoretical analyses of drug‐taking behavior posit an important mediating role for Pavlovian‐conditioned drug responses that develop as a result of stimulus‐drug pairings imbedded within the self‐administration paradigm. Some of these analyses focus attention on the learning of physiological responses that appear to counteract or compensate for the direct effects of a drug, thereby producing tolerance and encouraging increased drug taking. Others place greater emphasis on the learning of responses that mimic the drug's effect and presumably increase drug taking through a positive incentive mechanism. Our laboratory has been especially interested in the determinants of drug‐induced conditioned changes in body temperature and the roles that such responses might play in drug tolerance, sensitization, and self‐administration. Our research has involved both alcohol and morphine, drugs that produce a similar conditioned thermal response despite the fact that the direct thermal effects of these drug are completely different. In the case of alcohol, our initial studies showed that environmental (cage) cues paired with intraperitoneal (i.p.) injection of the drug acquire the ability to evoke a conditioned hyperthermic response that reduces the hypothermic reaction to ethanol (i.e., tolerance). More recent studies have explored the nature of the events capable of serving as conditioned stimuli (CSs) for such learning. These studies show that interoceptive thermal cues can mediate tolerance to alcohol's thermal effect, but taste cues cannot. The inability of taste cues to mediate tolerance may have special implications for the study of responses that are conditioned during oral self‐administration of alchol, a procedure that offers very salient gustatory cues. In the case of morphine, we have developed an experimental preparation that permits precise temporal control over the CS (a noise‐light compound) and unconditioned stimulus (intravenous morphine) while using techniques that minimize the stress that is induced by drug administration or temperature measurement. These studies show development of a conditioned hyperthermic response that summates with morphine‐induced hyperthermia, resulting in sensitization. The similarity in the conditioned thermal responses induced by alcohol and morphine has encouraged us to consider the possibility that these responses are not directly related to specific drug effects on the thermoregulatory system but instead reflect a nonspecific anticipatory “arousal” response. This notion receives some support from recent studies in our laboratory showing that environmental cues associated with non‐drug reinforcers differing in hedonic value (i.e., shock and sucrose) also acquire the ability to elicit conditioned hyperthermia. It could well be that drug‐induced conditioned changes in body temperature index the acquired motivational processes that maintain drug‐taking and encourage relapse.
- conditioned compensatory response
ASJC Scopus subject areas
- Drug Discovery