Sensitization of the locomotor response to psychostimulants after repeated opiate exposure: role of the nucleus accumbens.

The following experiments were performed to ascertain the role of the nucleus accumbens in opiate-dopamine interactions using measures of locomotor activity. Three separate experiments were carried out. In Experiment 1, rats received systemic morphine (10 mg/kg IP) or saline (1 ml/kg IP) every other day for 5 days, followed by systemic amphetamine (1.5 mg/kg) 48 hours following the fifth injection. Animals in the morphine pretreatment group exhibited a sensitized locomotor response to amphetamine. In Experiment 2, animals received the same systemic pretreatment and were subsequently given intraaccumbens saline, amphetamine (2.5 micrograms/0.5 microliter) or cocaine (7 micrograms/0.5 microliter), each separated by 48 hours. Morphine-pretreated animals showed enhanced motor activity in response to intraaccumbens microinfusion of the psychostimulant drugs. Finally, in Experiment 3, multiple microinjections of morphine (0.5 microgram/0.5 microliter) directly into the nucleus accumbens resulted in a potentiated locomotor response to intraaccumbens amphetamine (2.5 micrograms/0.5 microliter). These data indicate that the nucleus accumbens may contribute to both the development and expression of opiate-stimulant cross-sensitization. The neural basis of this sensitization is hypothesized to be a common intracellular pathway affected by both classes of drugs, such as the cyclic adenosine monophosphate (AMP) system.