DISULFIRAM CAUSES SUSTAINED BEHAVIORAL AND BIOCHEMICAL EFFECTS IN RATS

The present experiment examined effects of disulfiram (Antabuse(R)) ad ministration on behavioral measures of nociception (hot plate and tail flick), peripheral muscular performance (grip strength), motivated pe rformance, balance, and coordination (rotorod) in 24 male Sprague-Dawl ey rats during and 2 wk after an eight-day administration of disulfram . In addition, peptidylglycine alpha-hydroxylating monooxygenase (PHM) activity in several tissues and levels of alpha-amidated alpha-melano cyte stimulating hormone (alpha-MSH) in the neurointermediate lobe of the pituitary were assayed to evaluate biochemical effects of disulfir am. 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, o ccurred after one week of disulfiram administration. Decrements in gri p 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 underl ie decrements in grip strength. The present experiment provides a para digm for further investigations of effects of alpha-amidated peptides on behavior. Copyright (C) 1997 Elsevier Science Inc.