Chronic effects of clonazepam, phenytoin, ethosuximide, and valproic acid on learning in pigeons as assayed by a repeated acquisition procedure

The acute and chronic effects of the antiepileptic drugs clonazepam (0.06, 0.13, and 0.25 mg/kg), phenytoin (2.5, 5, 7.5 mg/kg), ethosuximide (40, 80, and 120 mg/kg), and valproic acid (40, 80, and 120 mg/kg) were evaluated in pigeons responding under a repeated acquisition procedure. At certain doses, acute administrations of all drugs impaired learning (i.e., increased errors) and reduced rate of responding. Appreciable tolerance developed to these effects with chronic exposure, although the physiological mechanism responsible for this outcome is unknown.