EFFECT OF ESEROLINE ON SCHEDULE-CONTROLLED BEHAVIOR IN THE RAT

Male Sprague-Dawley rats were trained to press a lever on a simple-alternation multiple fixed-ratio (FR) 20-response time-out (TO) schedule for water reinforcement. Twelve 5-min periods of FR reinforcement were each followed by a 5-min TO in which responding had no scheduled consequence. Doses ranging from 0.25 to 8 mg/kg of eseroline, the hydrolysis product of eserine and a potent analgesic agent with weak anticholinesterase activity, were administered SC immediately prior to a 120-min test session. Eseroline produced a dose-dependent monotonic decrease in the number of reinforcements, with significant effects at doses of 1, 2, 4 and 8 mg/kg and an ED50 of 2.5 (1.6-3.4) mg/kg. This behavioral disruption was characterized by a rapid onset of pausing (i.e., within 5 min postdosing) and a gradual recovery to normal baseline levels of responding over the remaining session time. The duration of the rate decreasing effects was dose-related with the highest dose having a mean duration of more than 60 min, which was longer than that of previous reports on antinociception produced by eseroline ( < 60 min). The coadministration of behaviorally inactive dose of the opiate antagonist naloxone (1 and 2 mg/kg, IP) with eseroline (2.5 mg/kg, ED50) antagonized the effects of eseroline on the operant behavior. The coadministration of behaviorally inactive doses of the muscarinic antagonist atropine with eseroline (2.5 mg/kg) did not effect eseroline's behavioral effect. These results suggest that the effects of eseroline on operant behavior is consistent with the effects of eseroline-induced antinociception, reported previously, and appears to be associated with the activation of opiate receptors, but not related to the stimulation of muscarinic receptors via its anticholinesterase activity.