Ultrastructural correlates of haloperidol-induced oral dyskinesias in rats: a study of unlabeled and enkephalin-labeled striatal terminals.
Chronic neuroleptic treatment in rats induces vacuous chewing movements (VCMs) that mimic tardive dyskinesia. Such treatment decreases overall striatal synaptic density, but rats with VCMs also have decreased density of symmetric synapses, indicating less inhibitory synaptic transmission. This study examined the striatum to determine if enkephalinergic terminals, which form symmetric synapses, are affected. All synapses combined, asymmetric and symmetric axospinous, and enkephalinergic synapses were significantly reduced in density in the haloperidol treated group as compared to controls. A loss of asymmetric axodendritic synapses, typical of excitatory thalamic inputs, was observed preferentially in the low VCM group. A loss of symmetric axodendritic synapses was observed preferentially in the high VCM group. This study indicates that a population of synapses, other than enkephalinergic ones, is preferentially lost in the high VCM group. Moreover, lack of VCMs may be due to changes in synaptic organization that are protective as well as the absence of pathologic connections.
Roberts
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RC
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA. Rroberts@mprc.umaryland.edu
Lapidus
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D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D003712:Dendrites / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004409:Dyskinesia, Drug-Induced / Q000473:pathology* / Q000503:physiopathology; D004745:Enkephalins / Q000378:metabolism*; D006220:Haloperidol / Q000633:toxicity*; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013570:Synaptic Membranes / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D013788:Thalamus / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
D014150:Antipsychotic Agents; D004745:Enkephalins; D006220:Haloperidol