ArticleMovement disorders : official journal of the Movement Disorder Society2026
Morphological Changes in Direct Pathway Striatal Neurons in a Rat Model of Tardive Dyskinesia.
Article in Movement disorders : official journal of the Movement Disorder Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundTardive dyskinesia (TD) and drug-induced parkinsonism (DIP) arise from prolonged dopamine antagonist use. Although D2 receptor hypersensitivity in the indirect pathway is a proposed mechanism, the role of the direct pathway remains unclear.
objectivesTo investigate morphological changes in the direct pathway striatal neurons' axon terminals in a rat model of haloperidol-induced TD and DIP.
methodsMale Wistar rats received haloperidol decanoate or placebo over 6 months. Behavioral tests assessed TD- and DIP-like symptoms. Axon terminals forming synapses on dendrites in the internal (GPi) and external (GPe) segments of the globus pallidus were analyzed using electron and immunoelectron microscopy.
resultsHaloperidol-treated rats exhibited both TD- and DIP-like behaviors. Vesicular gamma-aminobutyric acid (GABA) transporter (VGAT)-positive terminals were selectively enlarged in the GPi, and substance P colocalization indicated a direct pathway origin.
conclusionsStructural alterations in direct pathway nerve terminals may contribute to TD, challenging conventional models that focus solely on the indirect pathway. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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