Intraaccumbens raclopride attenuates amphetamine-induced locomotion, but fails to prevent the response-reinstating properties of food reinforcement.

It has been well established that the presentation of a single reinforced trial in the midst of extinction results in a reinstatement of the previously reinforced operant response. In previous experiments, we have shown that systemically applied raclopride (a selective dopamine D2 receptor antagonist) dose dependently blocked the response-reinstating properties of food reinforcement, while SCH39166 (a selective dopamine D1 receptor antagonist) did not (11). The current experiments investigated the possible role of the nucleus accumbens in these actions of raclopride. In the first of two experiments, hungry rats were trained to traverse a straight runway for food reinforcement, a response that was then weakened through a series of extinction trials. On a single treatment trial, subjects were infused with one of three doses of intraaccumbens raclopride (0.0, 2.5, or 5.0 microg/0.5 microl/side) just prior to a reinforced trial. Twenty-four hours later, a single test trial was run in an unbaited runway. The results demonstrate that the prior day's reinforced trial produced a reinstatement of operant runway performance that was unaltered by intraaccumbens applications of raclopride. Two days later, the same animals were tested in a second experiment investigating the effects of intraaccumbens raclopride on amphetamine-induced locomotion. Subjects were pretreated with 1.0 mg/kg s.c. amphetamine prior to a 90-min locomotor activity session. The following day, subjects were again pretreated with amphetamine, but this time with a challenge dose of raclopride. Results demonstrate that the same raclopride doses that produced no effect in the response-reinstating experiment produced, in the same rats, a dose-dependent attenuation in amphetamine-induced locomotion. These data suggest that dopamine D2 receptors in the nucleus accumbens may not, in and of themselves, be necessary for the response-reinstating effects of food reinforcement.