Long-term opiate effects on amphetamine-induced dopamine release in the nucleus accumbens core and conditioned place preference

Abstract

Withdrawal following chronic exposure to opiates or other drugs of abuse, administered as frequent doses, or a chronic infusion can cause reductions in mesolimbic dopamine (DA) transmission. However, mesolimbic DA transmission can be enhanced by opiates or psychostimulants administered intermittently as a single daily injection. Both enhanced and attenuated responsiveness of the mesolimbic DA system may have important implications for substance abuse disorders. Previous studies have shown that procedures that use electrical stimulation or drug treatments to augment neurotransmitter release are more effective for demonstrating declines in mesolimbic DA transmission that persist for extended periods following opiate withdrawal. The present study evaluated the effects of pretreatment with noncontingent morphine on amphetamine-induced DA release in the nucleus accumbens core and conditioned place preference (CPP). Morphine pretreatment was administered as a constant infusion, which was gradually increased to a dose of 50 mg/kg/day over a 1-week period in Wistar rats. At 10 days after cessation of morphine pretreatment, baseline dialysate DA levels in the nucleus accumbens core were unchanged, but amphetamine-induced increases in DA were attenuated by greater than 50% in morphine-pretreated animals. Morphine pretreatment did not modify locomotor activity during conditioning sessions, expressed as absolute values or change in activity counts between saline and morphine injections. Place preference, conditioned by two morphine pairings at 10 and 11 days after the onset of opiate withdrawal, was enhanced by opiate pretreatment between 12 and 33 days after the onset of withdrawal. In conclusion, morphine pretreatment delivered as a constant infusion can have pronounced and long-lasting effects on DA release and CPP, which may have important implications for drug-seeking behavior and treatment of substance abuse disorders.