Previous exposure to amphetamine increases incentive to obtain the drug: long-lasting effects revealed by the progressive ratio schedule

Abstract

The present experiment tested whether previous exposure to amphetamine would enhance rats’ predisposition to self-administer a high dose of the drug under fixed (FR) and progressive ratio (PR) schedules of reinforcement. Rats in different groups were given five injections of either amphetamine (1.5 mg/kg, i.p.) or saline (1.0 ml/kg, i.p.), one injection administered every third day and, starting 10 days later, given the opportunity to lever press for amphetamine (200 μg/kg/infusion, i.v.) on each of several 4 h sessions. When allowed to self-administer up to 10 infusions under first an FR-1 and then an FR-2 schedule, amphetamine and saline pre-exposed rats were indistinguishable and readily acquired the lever press response. However, when tested under the PR schedule of reinforcement, rats previously exposed to amphetamine achieved higher break points than saline pre-exposed rats across six consecutive PR sessions. This difference between groups was long lasting and durable. When compared to saline pre-exposed rats on three separate tests conducted 10, 14 and 21 days following the last PR session, rats pre-exposed to amphetamine also showed (i) greater nucleus accumbens dopamine reactivity to amphetamine (1.0 mg/kg, i.p.), (ii) higher break points when retested on the PR schedule, and (iii) a greater locomotor response to amphetamine (1.0 mg/kg, i.p.). On the last test, both groups showed higher levels of locomotion than no drug control animals that received amphetamine for the first time on this test. These findings suggest that previous exposure to amphetamine produces a long lasting enhancement in the incentive motivation animals will exhibit in their effort to obtain the drug. This enhancement appears to parallel sensitization of the drug’s locomotor and nucleus accumbens dopamine activating effects. It may very well be exacerbated by continued exposure to self-administered amphetamine.