Presently there is no established treatment for
antipsychotic drugs-induced
tardive dyskinesia (TD), which remains a major clinical issue in psychiatry. Based on the principles of the glutamatergic hypothesis of
schizophrenia, the
amino acid glycine (GLY) and the antituberculosis drug D-
cycloserine (DCS) have been assessed, during the last decade, as adjuvants to
antipsychotic drugs. Observations stemming from these studies suggest that, in addition to improving
schizophrenia symptoms, these compounds may also be beneficial against
drug-induced dyskinesias. In order to investigate this hypothesis, GLY and DCS effects were studied using the putative TD analogue vacuous chewing movements (VCM) rat model. Following 24 weeks of treatment with
haloperidol decanoate (0.38 mg/kg/4 weeks) rats (N=40) were randomized to receive one
intraperitoneal injection with 1.6 g/kg
GLY, 10 mg/kg ("low dose") DCS; 100 mg/kg ("high dose") DCS or saline ("placebo"), respectively. Behavior was videotaped at intervals during the experiment and all VCM, rearing, grooming and immobility episodes were analyzed and scored. A control group (N=9) received saline for 24 weeks.
Haloperidol administration decreased motor activity and significantly induced VCM. High dose DCS significantly reduced VCM without affecting other motor parameters. GLY treatment resulted in significantly less VCM but also reduced rearing, grooming and mobility. In contrast, low dose DCS and placebo did not significantly affect any of these parameters. These findings indicate that the use of GLY and DCS results in attenuation of VCM in rats and may have an effect on TD in humans. Clinical trials with this type of compounds for patients suffering from TD are warranted.