EMERGENCE OF ORAL AND LOCOMOTOR-ACTIVITY IN CHRONIC HALOPERIDOL-TREATED RATS FOLLOWING CORTICAL N-METHYL-D-ASPARTATE STIMULATION

Neuroleptic-induced orofacial movements in rats have been widely utili zed as an animal model of tardive dyskinesia (TD). The present study i nvestigated the role of the oral motor cortex in these movements by ap plying direct cortical stimulation in rats exposed to chronic haloperi dol. Rats received depot IM injections of haloperidol decanoate or ses ame oil vehicle every 3 weeks (10 rats per group). After 24 weeks of i njections and a 3-week withdrawal period, bilateral guide cannulae wer e implanted into the primary oral motor cortex. After a 1-week recover y, bilateral microinfusions of saline Vehicle followed by 1, 3, and 10 mM N-methyl-D-aspartate (NMDA) were given and observations of oral ac tivity, locomotion, rearing, and grooming were recorded. Haloperidol-t reated rats displayed a significant emergence of NMDA stimulated oral activity (nondirected oral movements, oral tremor, audible teeth grind ing, and directed oral movements). In addition, rearing and locomotion were significantly elevated in these animals. In contrast to haloperi dol-treated rats, sesame oil-treated rats showed no significant emerge nce of any motor activity. These results suggest that chronic haloperi dol administration alters primary motor cortex efferents, and that thi s effect may be a factor in the manifestation of chronic neuroleptic i nduced motor side effects, such as TD. (C) 1998 Elsevier Science Inc.