Abstract
The development of vacuous chewing movements (VCMs), and changes in glutamic acid decarboxylase (GAD) and choline acetyltransferase (ChAT) activities in extrapyramidal nuclei were examined in rats treated chronically with neuroleptics. Animals were injected with flupenthixol (FLU) or haloperidol (HAL) decanoate for 16, 40 or 48 weeks and were then sacrificed. Another group of rats was treated with FLU or HAL for 48 weeks, and then withdrawn from the neuroleptics for 16 weeks before sacrifice. VCMs were assessed weekly, and the effects of the GABA agonist progabide on VCMs and locomotor activity were examined. GAD and ChAT activities were determined at death. The concentrations of Calbindin D28K (CaBP) and parvalbumin (PV) were determined in rats receiving 48 weeks of neuroleptic treatment. VCMs first appeared after 8–10 weeks of neuroleptic administration, reached asymptotic rates after 18–20 weeks, and then remained stable for the remainder of the chronic drug administration period. During withdrawal, there was a steady decline in the VCM rate. The GABA receptor agonist progabide reduced VCMs and locomotor activity. Significant decreases in nigral GAD activity were observed after 40, but not after either 16 or 48 weeks of neuroleptic administration. CaBP and PV were unchanged after 48 weeks of neuroleptic treatment. In addition, ChAT activities in 16, 40 or 48 week treated animals did not show consistent changes after either neuroleptic. Chronic neuroleptic administration followed by 16 weeks of withdrawal also did not have any significant effects on GAD or ChAT activity in any of the brain areas examined. The present results demonstrate that decreases in nigral GAD activity do not occur when VCMs have reached near maximal rates. It appears, therefore, that neuroleptic-induced VCMs and decreases in nigral GAD activity are not causally related. Nevertheless, the reduction in VCMs produced by progabide suggests that impaired GA-BAergic mechanisms may be involved in the expression of these abnormal perioral movements.
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Mithani, S., Atmadja, S., Baimbridge, K.G. et al. Neuroleptic-induced oral dyskinesias: effects of progabide and lack of correlation with regional changes in glutamic acid decarboxylase and choline acetyltransferase activities. Psychopharmacology 93, 94–100 (1987). https://doi.org/10.1007/BF02439593
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DOI: https://doi.org/10.1007/BF02439593