Disulfiram causes sustained behavioral and biochemical effects in rats

The present experiment examined effects of disulfiram (Antabuse) administration on behavioral measures of nociception (hot plate and tail flick), peripheral muscular performance (grip strength), motivated performance, balance, and coordination (rotorod) in 24 male Sprague-Dawley rats during and 2 wk after an eight-day administration of disulfiram. In addition, peptidylglycine 5(-hydroxylating monooxygenase (PHM) activity in several tissues and levels of alpha-amidated alpha-melanocyte stimulating hormone (alpha-MSH) in the neurointermediate lobe of the pituitary were assayed to evaluate biochemical effects of disulfiram. These particular assays were included because it has been reported that disulfiram affects alpha-amidated peptides via alteration of PHM activity. Decrements in all behavioral measures, except tail flick, occurred after one week of disulfiram administration. Decrements in grip strength continued for the 2 wk after cessation of disulfiram. Dose-related reductions in changes in PHM activity and levels of alpha-MSH were found 2 wk after cessation of disulfiram administration. The time course of the results suggest that changes in PHM activity may underlie decrements in grip strength. The present experiment provides a paradigm for further investigations of effects of alpha-amidated peptides on behavior.