THE EFFECTS OF ETICLOPRIDE NAD NALTREXONE ON RESPONDING MAINTAINED BYFOOD, COCAINE, HEROIN AND COCAINE HEROIN COMBINATIONS IN RATS/

In the first experiment, responding was maintained for food under a fi xed ratio (FR) 10 with a 6-min timeout reinforcement schedule. Eticlop ride (0.1-1.0 mg/kg i.p.) dose-dependently decreased the number of foo d pellets obtained, whereas naltrexone (3-30 mg/kg i.p.) did not signi ficantly alter responding. In the second experiment, intravenous self- administration of cocaine (vehicle, 125, 250 and 500 mu g/infusion), h eroin (vehicle, 5.4, 9 and 18 mu g/infusion) and cocaine/heroin combin ations were maintained under a FRIO reinforcement schedule. Cocaine/he roin combinations included the aforementioned cocaine doses combined w ith 5.4 mu g/infusion heroin (CH5.4) or 18 mu g/infusion heroin (CH18) . Cocaine/heroin combinations dose dependently decreased the number of infusions compared with cocaine alone. Eticlopride (0.03-0.3 mg/kg i. p.) decreased self-administration of 125 mu g/infusion cocaine and inc reased self-administration of 500 mu g/infusion cocaine. Self-administ ration of 250 mu g/infusion cocaine was increased after 0.03 and 0.1 m g/kg and decreased after 0.3 mg/kg eticlopride. Eticlopride decreased heroin self-administration, an effect which may be attributable to its rate-decreasing effects. Eticlopride partially reversed the downward shift of the CH5.4 group but did not reverse the effects in the CH18 g roup. Naltrexone (1.0-10.0 mg/kg i.p.) decreased self-administration o f 5.4 mu g/infusion heroin and increased self-administration of 18 mu g/infusion heroin, Self-administration of 9 mu g/infusion heroin was i ncreased by 1.0 mg/kg, not affected by 3.0 mg/kg and decreased by 10.0 mg/kg naltrexone. For the CH5.4 and CH18 groups, naltrexone dose-depe ndently shifted the dose-effect curves toward the cocaine dose-effect curve. Therefore, self-administration of cocaine/heroin combinations c an be maintained in the rat and downward shifts in the cocaine dose-ef fect curve after combination with heroin are mediated through a naltre xone-sensitive mechanism.