Reduced number of striatal neurons expressing preprosomatostatin mRNA in rats with oral dyskinesias after long-term haloperidol administration

Neuroleptic-induced oral dyskinesia in rats, a putative analogue to human t ardive dyskinesia, may be due to degeneration within the striatum. Using un biased stereological methods, a decreased number of striatal neurons expres sing preprosomatostatin mRNA was observed only in rats that developed prono unced oral dyskinesias after 30 weeks of haloperidol administration. The am ount of preprosomatostatin mRNA in each striatal neuron, measured in terms of optical densities of individual neurons, was not affected by haloperidol . A tendency toward a reduction in the number of NADPH-diaphorase positive neurons was observed in rats receiving haloperidol. These results indicate that the mechanism by which neuroleptics induce oral dyskinesias in rats, a nd perhaps tardive dyskinesia in humans, involves a functional disruption a nd possibly damage of a subpopulation of interneurons in the striatum. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.