title: Neuroleptic-induced oral dyskinesias: effects of progabide and lack of correlation with regional changes in glutamic acid decarboxylase and choline acetyltransferase activities.
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 Another group of rats was treated with FLU or HAL for 48 weeks, and then withdrawn from the neuroleptics for 16 weeks before sacrifice.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.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000201:enzymology; D005475:Flupenthixol / Q000031:analogs & derivatives / Q000633:toxicity; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006220:Haloperidol / Q000633:toxicity; D008297:Male; D008409:Mastication / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D010320:Parvalbumins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; C017985:progabide; C007761:flupenthixol decanoate; D005680:gamma-Aminobutyric Acid; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D005475:Flupenthixol; D006220:Haloperidol