SIGNALED VERSUS UNSIGNALED INTRAVENOUS AMPHETAMINE - LARGE DIFFERENCES IN THE ACUTE PSYCHOMOTOR RESPONSE AND SENSITIZATION

Both the acute psychomotor response and the development of sensitizati on to amphetamine are attenuated if i.p. injections are given in the c age where animals live (HOME), relative to when injections are given i n a novel (NOVEL), but otherwise physically identical cage. It was sug gested that this effect of environment on sensitization may be due to the relative availability of cues predictive of drug administration in the two conditions. It was hypothesized, therefore, that removal of a ll environmental cues predictive of drug administration would attenuat e the development of sensitization even further. This was accomplished by comparing the psychomotor activating effects (rotational behavior) of repeated unsignalled intravenous (i.v.) infusions of 1.0 mg/kg amp hetamine given in a HOME environment with those of signalled i.v. infu sions given in a NOVEL environment. It was found that signalled i.v. a mphetamine administration (NOVEL) produced a large acute psychomotor r esponse, and repeated administrations resulted in a significant increa se in psychomotor response (i.e., sensitization). In contrast, the sam e treatment in the HOME condition produced only a very small acute res ponse and no sensitization. Indeed, the magnitude of the psychomotor r esponse to an amphetamine challenge varied approximately 23-fold as a function of past drug history and environmental condition. It is sugge sted that this paradigm provides a powerful new model to study how env ironmental factors modulate responsiveness to psychoactive drugs.