ENDURING ENHANCEMENT OF AMPHETAMINE SENSITIZATION BY DRUG-ASSOCIATED ENVIRONMENTAL STIMULI

We report on the effect of environment on amphetamine sensitization in rats with a unilateral 6-hydroxydopamine lesion of the mesostriatal d opamine system. The rats were either housed in the test environment (H OME) or exposed to it only during the treatments (NOVEL). In experimen t I, the rats received seven consecutive i.p. injections of either sal ine or 2 mg/kg amphetamine. After 1 wk withdrawal the rotational respo nse to 2 mg/kg amphetamine i.p. (i.e., amphetamine challenge) was comp ared in saline-vs, amphetamine-pretreated animals. Although both HOME and NOVEL groups sensitized, the magnitude of sensitization was greate r in the NOVEL group. In the NOVEL group there was also a greater cond itioned response to drug-related cues. In experiment 2 a dose-effect c urve (0.75, 1.5, 3.0 and 6.0 mg/kg amphetamine i.p.) was determined be fore and after six i.p. injections of 4.0 mg/kg amphetamine. Sensitiza tion was indicated by a parallel shift to the left of the dose-effect curve in both groups, but this shift was 2.6 times greater in the NOVE L group than in the HOME group. Finally, in experiment 3, we found tha t environment-and sensitization-dependent differences in the psychomot or response to amphetamine were not accompanied by differences in the concentration of amphetamine in the plasma or in the striatum.