Naloxone reduces the neurochemical and behavioral effects of amphetamine but not those of cocaine.

The specific opioid receptor antagonist naloxone modifies the effects of amphetamine in a wide variety of behavioral paradigms. Naloxone also attenuates the amphetamine-induced increase in extracellular dopamine in the brain of rats. Therefore, these experiments were designed to replicate the neurochemical and behavioral interactions between naloxone and amphetamine, and to extend these observations to interactions between naloxone and cocaine. Microdialysis was performed on adult male rats of Sprague-Dawley descent. Rats were pretreated with a subcutaneous injection of 5.0 mg/kg naloxone or vehicle, which was followed 30 min later by cumulative doses of subcutaneous d-amphetamine (0.0, 0.1, 0.4, 1.6, 6.4 mg/kg) or intraperitoneal cocaine (0, 3, 10, 30, 56 mg/kg) at 30 min intervals. The microdialysis probes were perfused at a flow rate of 0.6 microliter/min with artificial cerebrospinal fluid. Dialysate samples were collected every 10 min from either the nucleus accumbens or striatum and analyzed for dopamine content by high-performance liquid chromatography (HPLC). Locomotor activity (photobeam breaks) was monitored simultaneously with the collection of dialysate samples. Amphetamine and cocaine dose-dependently increased extracellular dopamine in both the nucleus accumbens and striatum. Naloxone pretreatment significantly reduced the amphetamine-induced increase in extracellular dopamine in both brain regions and also attenuated the increase in locomotor activity elicited by amphetamine. Naloxone pretreatment had no effect, however, on the cocaine-induced increase in extracellular dopamine or locomotor activity. These findings suggest that endogenous opioid systems play a role in mediating the neurochemical and behavioral effects of amphetamine, but not those of cocaine.