Effects of naltrexone on intravenous cocaine self-administration in rats during food satiation and deprivation

Rats self-administered i.v. delivered cocaine (0.1 mg/kg) under conditions of continuous access (session length 24 hr). Each lever press resulted in an infusion according to a fixed-ratio 1 schedule. Food was continuously available except for every third session, when the rats were food deprived, i.e., provided with only 8 g at the start of the session. After behavior stabilized, the rats were given naltrexone (N), saline (V) or no injections (O) on successive days according to the following sequence: N, V, O, V, N, O.... This sequence began on a food deprivation session and repeated until four naltrexone and four saline injections had been given during both food satiation and deprivation sessions, although data were reported from only the last three sessions under each condition. Injections were given at the start of the session and after 7 hr of the session had elapsed. Cocaine was then replaced by saline for approximately half the rats, and the entire injection sequence was repeated until three naltrexone and three saline pretreatment sessions were completed during both food satiation and deprivation. Three separate groups of 9 or 10 rats each received a different dose of naltrexone (0.5, 1 or 2 mg/kg i.v.). As reported earlier, cocaine- and saline-reinforced responding increased more than 2-fold during food deprivation. During food satiation, naltrexone pretreatment nearly doubled cocaine self-administration, with the greatest increase at the 1-mg/kg naltrexone dose. Naltrexone had no systematic effect on cocaine-reinforced responding during food deprivation, and it had no effect on saline-maintained responding during food satiation or deprivation. Naltrexone also produced excessive salivation, rhinorrhea and diarrhea as well as a characteristic posture during cocaine self-administration.