Differential role of delta-opioid receptors in the development and expression of behavioral sensitization to cocaine.

The present study was designed to determine whether the selective delta-opioid receptor antagonist naltrindole hydrochloride can prevent the expression and development of sensitization to the locomotor-activating effects of cocaine. Rats were sensitized to the motor stimulant effects of cocaine (20 mg/kg i.p. x 3 days). 48 h after withdrawal of pretreatment, rats were pretreated with naltrindole (0.1-1.0 mg/kg s.c.) or its vehicle and 15 min later challenged with either saline or the sensitizing dose of cocaine. In a second set of experiments, naltrindole (0.1-1.0 mg/kg s.c.) or its vehicle were given in combination with either saline or cocaine (20 mg/kg i.p.) for 3 days. Activity in response to saline and to cocaine (20 mg/kg i.p.) was assessed on days 4 and 5, respectively. Additional experiments determined whether naltrindole prevents the development of sensitization to the locomotor-activating effects of nicotine: naltrindole (0.3, 1.0 mg/kg s.c.) or its vehicle were given in combination with nicotine (0.6 mg/kg s.c.) for 3 days. Naltrindole blocked the development but not expression of sensitization to the locomotor-activating effects of cocaine. In contrast, naltrindole failed to modify nicotine-induced sensitization in nicotine-treated animals. These data suggest that delta-opioid receptors are involved in the development but not expression of behavioral sensitization to cocaine.