The nullification by diazepam of haloperidol-induced increases in the level of striatal dopamine but not in the activity of glutamic acid decarboxylase.

In the therapeutic management of neuroleptic-induced tardive dyskinesia, diazepam, baclofen or gamma-vinyl-gamma-aminobutyric acid have been advocated. It has been postulated, but not proven, that the beneficial effects of these agents in tardive dyskinesia may be mediated by enhancing GABAergic transmission. In this study, it is reported that, during a 3-day withdrawal period following daily administration of 3 mg/kg of haloperidol (i.p.) for 3 weeks, the activity of glutamic acid decarboxylase in the striatum increased from 72.6 +/- 7.8 to 92.5 +/- 10.2 nmol 14CO2/mg protein/hr, and the concentration of dopamine in the striatum increased from 7.87 +/- 0.23 to 8.86 +/- 0.38 micrograms/g wet tissue. Diazepam (5 mg/kg, i.p.), given during the withdrawal period from haloperidol was able to nullify the enhancement in the concentration of dopamine but not in the activity of glutamic acid decarboxylase in the striatum. The results of these studies are interpreted to indicate that the reported beneficial effects of diazepam and GABA-mimetic agents in ameliorating the symptoms of tardive dyskinesia may occur through a mechanism which does not necessarily link transmission involving both dopamine and GABA.