BehavioraL and biochemical changes caused by muscimol in mice withdrawN from haloperidol administration

This study was designed to determine the behavioral and biochemical effects of the gamma-aminobutyric acid (GABA) agonist, muscimol, in mice withdrawn from chronic haloperidol administration. Mice received either haloperidol or vehicle In their drinking water for 35 days, after which the haloperidol was replaced with vehicle. Seven days after withdrawal from chronic treatment with haloperidol, the effect of apomorphine on the climbing behavior of haloperidol-withdrawn mice was markedly enhanced as compared to control mice that received only vehicle. Muscimol produced a dose-related reduction in the intensity of climbing behavior induced by apomorphine in both control and haloperidol-withdrawn mice. However, the inhibition of climbing behavior induced by muscimol was significantly greater in haloperidol-withdrawn animals. In addition, in haloperidol-withdrawn mice, muscimol produced a significant reduction in striatal homovanillic (HVA) levels with no change in striatal dopamine (DA) levels, suggesting a decrease in DA turnover. In support of this conclusion, muscimol decreased the disappearance of dopamine in haloperidol-withdrawn mice that were injected with alpha-methyl-p-tyrosine. Both the behavioral and biochemical effects of muscimol were blocked by the GABA antagonist, picrotoxin. These results indicate that after chronic haloperidol administration there is not only an enhanced response to dopaminergic agonists but also to GABAergic agonists.