Inhibition of cocaine-induced sensitization by the delta-opioid receptor antagonist naltrindole.

The influence of the delta-opioid receptor antagonist naltrindole upon sensitization to the locomotor activating effects of cocaine was assessed. Activity in response to a challenge dose of cocaine (20 mg/kg, i.p.) was significantly increased in rats which had received cocaine (20 mg/kg, i.p.) once daily for 3 days as compared to those which had previously received saline. The repeated administration of naltrindole (0.3-3.0 mg/kg, s.c.) alone did not affect activity. However, in animals which had received both naltrindole and cocaine for 3 days, no sensitization to the locomotor activating effects of cocaine was observed. These data demonstrate that the selective blockade of delta-opioid receptors modifies the development of cocaine-induced sensitization and suggest an important role of delta-opioid receptor systems in modulating the development of drug-induced sensitization.