Controlling interindividual differences in the unconditioned response to amphetamine in the study of environment-dependent sensitization

Abstract

Two subgroups of rats selected on the basis of their emergence latency in a light-dark box test were shown to exhibit significantly different unconditioned responses to d-amphetamine (AMPH, 1mg/kg). The rats presenting a low latency to emerge from the dark side (LL subgroup) responded more to AMPH than the rats presenting a high latency (HL subgroup). These two subgroups were compared for environment-dependent and environment-independent sensitization. The major findings were as follows: (a) when these two subgroups underwent a conditioning procedure to study environment-dependent sensitization, in which the paired groups received AMPH in Environment A (activity cages) and saline in Environment B (plastic housing cages), the unpaired groups received saline in A and AMPH in B, and the control groups received saline in both environments, only the LL subgroup showed conditioned activity and environment-dependent sensitization; (b) when LL and HL subgroups were submitted to a sensitization procedure designed to rule out any conditioning processes (environment-independent sensitization), there was no significant difference in the development and magnitude of sensitization although the amplitude of the response following each injection remained lower in the HL compared with the LL subgroup; (c) when unconditioned responses to AMPH for the two subgroups were equated by increasing the dose of AMPH for the HL rats (1.25mg/kg), there was no longer a significant difference between the two subgroups with respect to conditioned activity and environment-dependent sensitization; (d) in the LL subgroup, an extinction procedure (in which all animals received vehicle in both environments) that completely abolished the conditioned activity in the paired group, suppressed the difference between paired and unpaired groups during the test for environment-dependent sensitization, by reducing the response of the former. Overall, these results provide two major contributions: first, they show that interindividual differences in the unconditioned response to AMPH influence the outcome of the study of environment-dependent sensitization; second, when these differences are controlled, they suggest that environment-dependent sensitization appears to be the result of the addition between conditioned activity and environment-independent effects of AMPH.