Cyclazocine disruption of operant behavior is antagonized by naloxone and metergoline

Male-Sprague-Dawley rats were trained to press a lever on a fixed ratio-40 (FR-40) schedule for food reinforcement. Doses ranging from 0.5 to 16 mg/kg of the mixed narcotic agonist-antagonist cyclazocine (30-min pretreatment) resulted in a dose-dependent decrease in the number of reinforcements obtained and a reciprocal increase in “pausing” (IRT's greater than 10 sec). A 5-min pretreatment with 4 mg/kg of the narcotic antagonist naloxone attenuated the cyclazocine disruption. The 5-HT antagonist metergoline (1 mg/kg; 180-min pretreatment) also blocked cyclazocine effects to approximately the same degree as did naloxone. However, the shift of the dose response pattern of cyclazocine was not parallel for either antagonist. A greater degree of attenuation of the cyclazocine effects was observed when naloxone (4 mg/kg) and metergoline (0.1 mg/kg) were given together, indicating that cyclazocine disruption may be antagonized by either a narcotic antagonist or a 5-HT antagonist, and that these antagonists may operate synergistically. Thus, the behavioral effects of cyclazocine may relate to both opioid and serotonergic components.