Repeated pre-trial and post-trial low and high dose apomorphine treatments induce comparable inhibitory/excitatory sensitization and conditioned drug effects

Abstract

This investigation was undertaken to compare the sensitization/conditioned effects induced by apomorphine given pre-trial versus administered immediately post-trial or 15 min post-trial. We measured the effects on locomotor activity of 5 daily apomorphine treatments induced by an inhibitory low auto-receptor dose (0.05 mg/kg) and a stimulatory high postsynaptic dose (2.0 mg/kg). Three sets of four groups were used and each set of four groups was comprised of two vehicle and two apomorphine groups (0.05/2.0 apomorphine). The only difference among the three sets of four groups was when the treatments were administered relative to placement in the novel environment. One set received the treatment pre-test, another set was injected immediately after and the third set injected 15 min after 5 min test sessions in a novel environment. The repeated pre and immediate post-test apomorphine treatments induced locomotor sensitization over the 5 days of treatment. The low dose pre and immediate post-test treatments progressively decreased locomotion and the high dose pre and immediate post-test progressively increased locomotion. Critically, the tests for the immediate post-test groups were non-drug and for both the pre-test and immediate post-test groups, sensitization effects did not occur until the second test day. To control for non-associative apomorphine effects, the same apomorphine treatments were given post-test after a 15 minute delay and were found to be equivalent to vehicle. In a subsequent conditioning test, both the pre and immediate post-test low dose apomorphine groups showed conditioned behavioral inhibition and the pre and immediate post-test high dose apomorphine groups showed conditioned behavioral stimulation. We propose that the inhibitory low dose apomorphine decreased the salience/incentive of the novel environment association and thereby decreased the behavioral response and conversely that the high dose excitatory apomorphine treatment increased the salience/incentive value of the novel environment association and potentiated the behavioral response.