Previous Exposure to VTA Amphetamine Enhances Cocaine Self-administration under a Progressive Ratio Schedule in a D1 Dopamine Receptor Dependent Manner

Abstract

The effect of previous exposure to amphetamine (AMPH) in the ventral tegmental area (VTA) on the subsequent self-administration of cocaine was assessed. Rats in different groups were pre-exposed to three injections into the VTA of either saline (0.5μl/side) or AMPH (2.5μg/0.5μl/side). Injections were given once every third day. Starting 7–10 days after the last pre-exposure injection, rats were trained to self-administer cocaine (0.3 mg/kg/infusion) under fixed ratio 1 and 2 (FR1 and FR2) schedules and then tested under a progressive ratio (PR) schedule of reinforcement for six consecutive days. No differences between groups were observed during self-administration training under the FR schedules of reinforcement. However, when tested under the PR schedule, VTA AMPH pre-exposed rats worked more and, as a result, obtained more infusions of cocaine than saline pre-exposed rats. Rats in a separate group pre-exposed to VTA AMPH but co-infused with the D1-like dopamine (DA) receptor antagonist SCH23390 (0.25 μg/0.5μl/side) did not show enhanced cocaine self-administration. These rats, as well as others pre-exposed to VTA SCH23390 alone showed levels of cocaine self-administration similar to saline pre-exposed rats. Thus, in a manner paralleling the sensitization of AMPH-induced locomotion and nucleus accumbens DA overflow, previous exposure to AMPH in the VTA leads to enhanced intravenous self-administration of cocaine and activation of D1 DA receptors in this site during pre-exposure is necessary for the production of this effect.

DOI: 10.1016/S0893-133X(02)00379-2
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@article{Suto2002PreviousET, title={Previous Exposure to VTA Amphetamine Enhances Cocaine Self-administration under a Progressive Ratio Schedule in a D1 Dopamine Receptor Dependent Manner}, author={Nobuyoshi Suto and J D Austin and L M Tanabe and M Kramer and D Wright and Paul Vezina}, journal={Neuropsychopharmacology}, year={2002}, volume={27}, pages={970-979} }