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 utilized as an animal model of tardive dyskinesia (TD). The present study investigated the role of the oral motor cortex in these movements by applying direct cortical stimulation in rats exposed to chronic haloperidol. Rats received depot i.m. injections of haloperidol decanoate or sesame oil vehicle every 3 weeks (10 rats per group). After 24 weeks of injections and a 3-week withdrawal period, bilateral guide cannulae were implanted into the primary oral motor cortex. After a 1-week recovery, bilateral microinfusions of saline vehicle followed by 1, 3, and 10 mM N-methyl-D-aspartate (NMDA) were given and observations of oral activity, locomotion, rearing, and grooming were recorded. Haloperidol-treated rats displayed a significant emergence of NMDA stimulated oral activity (nondirected oral movements, oral tremor, audible teeth grinding, and directed oral movements). In addition, rearing and locomotion were significantly elevated in these animals. In contrast to haloperidol-treated rats, sesame oil-treated rats showed no significant emergence of any motor activity. These results suggest that chronic haloperidol administration alters primary motor cortex efferents, and that this effect may be a factor in the manifestation of chronic neuroleptic induced motor side effects, such as TD.