Memory re-consolidation and drug conditioning: An apomorphine conditioned locomotor stimulant response can be enhanced or reversed by a single high versus low apomorphine post-trial treatment

摘要

Rationale Psychostimulant sensitization can have transformative effects upon contextual stimuli such as acquired conditioned stimuli and conditioned incentive motivational properties. Objective The aim of this study is to induce apomorphine sensitization and conduct non-drug exposures to the contextual cues followed by post-trial treatments designed to associate increases/decreases in dopamine activity with re-consolidation of the contextual cue conditioned stimulus. Methods Separate groups received five daily apomorphine (2.0 mg/kg) treatments, paired or unpaired to the test environment. Two days later, a 30-min non-drug conditioning test was performed. Subsequently, there were three brief (5 min) conditioning tests on successive days. After removal from the test environment on the three test days, all groups received post-trial treatment with vehicle, 0.05, and 2.0 mg/kg apomorphine. One day later, a second 30-min conditioning test was conducted. Results There was a sensitized and a conditioned locomotor stimulant response in the paired groups. After the first and second post-trial treatments with 0.05 mg/kg apomorphine, the conditioned stimulant response in the paired group was transformed into a conditioned inhibitory response. In contrast, the conditioned stimulant response of the paired group administered with apomorphine 2.0 mg/kg post-trial was amplified. The apomorphine post-trial treatments administered to the unpaired groups or 2 h post-trial to paired groups were without effect. Conclusions These findings suggest that sensitization substantially enhances the associative sensitivity of contextual stimuli and imply that brief exposure to cues linked to drugs of addiction followed by treatments that inhibit neurotransmitter systems may provide a new direction in drug abuse treatment.