Differential effects of delta- and mu-opioid receptor antagonists on the amphetamine-induced increase in extracellular dopamine in striatum and nucleus accumbens

Abstract

The specific opioid receptor antagonist naloxone attenuates the behavioral and neurochemical effects of amphetamine. Furthermore, the amphetamine-induced increase in locomotor activity is attenuated by intracisternally administered naltrindole, a selective delta-opioid receptor antagonist, but not by the irreversible mu-opioid receptor antagonist beta-funaltrexamine. Therefore, this research was designed to determine if naltrindole would attenuate the neurochemical response to amphetamine as it did the behavioral response. In vivo microdialysis was used to monitor the change in extracellular concentrations of dopamine in awake rats. Naltrindole (3.0, 10, or 30 micrograms) or vehicle was given 15 min before and beta-funaltrexamine (10 micrograms) or vehicle 24 h before the start of cumulative dosing, intracisternally in a 10-microliters volume, while the rats were lightly anesthetized with methoxyflurane. Cumulative doses of subcutaneous d-amphetamine (0.0, 0.1, 0.4, 1.6, and 6.4 mg/kg) followed pretreatment injections at 30-min intervals. Dialysate samples were collected every 10 min from either the striatum or nucleus accumbens and analyzed for dopamine content by HPLC. Amphetamine dose-dependently increased dopamine content in both the striatum and nucleus accumbens, as reported previously. Naltrindole (3.0, 10, and 30 micrograms) significantly reduced the dopamine response to amphetamine in the striatum. In contrast, 30 micrograms of naltrindole did not modify the dopamine response to amphetamine in the nucleus accumbens. On the other hand, beta-funaltrexamine (10 micrograms) had no effect in the striatum but significantly attenuated the amphetamine-induced increase in extracellular dopamine content in the nucleus accumbens. These data suggest that delta-opioid receptors play a relatively larger role than mu-opioid receptors in mediating the amphetamine-induced increase in extracellular dopamine content in the striatum, whereas mu-opioid receptors play a larger role in mediating these effects in the nucleus accumbens.