Melanocyte-stimulating hormone and persistent tardive dyskinesia: a hypothesis.

An increased incidence of abnormal perioral movements has recently been reported in drug-naive pinealectomized rats with further accentuation of these movements following administration of haloperidol. Analysis of the temporal course of the development of the perioral dyskinetic movements revealed that the onset of these movements occurred within 4 days postoperatively and peaked at 3 weeks to plateau over the following 4-6 weeks. Increased pituitary Melanocyte-stimulating hormone (MSH) content has been reported in pinealectomized rats. Elevation of MSH content in the pinealectomized rats occurred within 3 days of surgery and was followed by normalization within 4 weeks. These findings suggest that compensatory mechanisms involving hypothalamic-pituitary MSH release must have been activated to induce normalization of pituitary MSH levels. Moreover, reduction of pituitary MSH levels may have coincided with attenuation in the severity of the perioral dyskinetic movements. It is possible that the development of tardive dyskinesia (TD) may in part be associated with increased brain and plasma MSH levels and that impaired hypothalamic-pituitary regulatory mechanisms of MSH release may be associated with persistent TD. The pineal gland may be implicated in this process as diminished melatonin secretion may be associated with disinhibition of MSH release. Thus, the above hypothesis complements and extends the recently presented "melatonin hypothesis" and suggests that research of pineal-hypothalamic interactions may be crucial to the further understanding of TD.