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 dopamine system. The rats were either housed in the test environment (HOME) or exposed to it only during the treatments (NOVEL). In experiment 1, the rats received seven consecutive i.p. injections of either saline or 2 mg/kg amphetamine. After 1 wk withdrawal the rotational response to 2 mg/kg amphetamine i.p. (i.e., amphetamine challenge) was compared in saline- vs. amphetamine-pretreated animals. Although both HOME and NOVEL groups sensitized, the magnitude of sensitization was greater in the NOVEL group. In the NOVEL group there was also a greater conditioned response to drug-related cues. In experiment 2 a dose-effect curve (0.75, 1.5, 3.0 and 6.0 mg/kg amphetamine i.p.) was determined before and after six i.p. injections of 4.0 mg/kg amphetamine. Sensitization 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 NOVEL group than in the HOME group. Finally, in experiment 3, we found that environment- and sensitization-dependent differences in the psychomotor response to amphetamine were not accompanied by differences in the concentration of amphetamine in the plasma or in the striatum.