The Effects of Acute and Repeated Pyridostigmine Bromide Administration on Response Acquisition with Immediate and Delayed Reinforcement

VAN HAAREN, F., R. DE JONGH, J. B. HOY, J. L. KARLIX, C. J. SCHMIDT, I. R. TEBBETT AND D.WIELBO. The effects of acute and repeated pyridostigmine bromide administration on response acquisition with immediate and delayed reinforcement. PHARMACOL BIOCHEM BEHAV 62(2) 389–394, 1999.—This experiment was designed to assess the effects of acute and repeated administration of pyridostigmine bromide (a carbamate with prophylactic and therapeutic uses) on response acquisition. Experimentally naı̈ve, male Sprague–Dawley rats were exposed to a situation in which lever presses were either immediately followed by food-pellet presentation or after a 16-s resetting delay. Different groups of rats received either one acute administration of pyridostigmine bromide (10 mg/kg, by gavage) or repeated pyridostigmine administration for 7 days (1.5 mg/kg/day, by gavage). Other groups were treated with distilled water for the same period of time. Both acute and repeated pyridostigmine bromide administration decreased serum cholinesterase levels by approximately 50%, but neither treatment affected brain cholinesterase levels in our assay. Acute and repeated drug administration produced the same behavioral effects. Subjects exposed to the 0-s delay conditions obtained many more food pellets than those exposed to the 16-s delay conditions. Administration of pyridostigmine bromide delayed the onset of responding in some, but not all, of the subjects in the treated groups, independent of the delay condition to which they were exposed. Many more responses were observed on an inoperative lever during the 16-s delay conditions than during the 0-s delay conditions, especially during the 16-s delay condition in which subjects had received acute vehicle administration. Whether or not these effects of small doses of pyridostigmine bromide on response acquisition are of central or peripheral origin will need to be determined in future studies, as response acquisition in the present experiment may have been affected by pyridostigmine’s effects on gastrointestinal functioning and/or motor activity.