Pharmacological Induction and Modulation of Catalepsy: A Comparative Analysis of Dopaminergic and Non-Dopaminergic Pathways

Abstract

Background:

Catalepsy is a neurophysiological condition characterized by muscular rigidity, diminished responsiveness to external stimuli, and maintenance of abnormal postures. It serves as a critical experimental model in preclinical studies, especially for evaluating extrapyramidal side effects of antipsychotic drugs and exploring Parkinsonism-related mechanisms. The dopaminergic system, particularly D2 receptor antagonism, has long been associated with cataleptic manifestations. However, growing evidence highlights the contribution of non-dopaminergic pathways, including cholinergic, GABAergic, glutamatergic, serotonergic, and opioid systems.

This review synthesizes and compares existing literature on the pharmacological induction and modulation of catalepsy via dopaminergic and non-dopaminergic pathways. Databases such as PubMed, Scopus, and ScienceDirect were searched using terms like “catalepsy,” “dopamine antagonists,” “neurotransmitters,” and “animal models of Parkinsonism.” Studies were selected based on relevance, methodological rigor, and recency.Dopaminergic antagonists such as haloperidol reliably induce catalepsy by blocking D2 receptors in the striatum. In contrast, non-dopaminergic agents affect cataleptic states by modulating neurotransmitter balance. Cholinergic agonists exacerbate catalepsy, whereas anticholinergics attenuate it. GABAergic and serotonergic systems exhibit a dual modulatory effect depending on receptor subtype and dose. The interaction between these pathways reveals a complex network regulating motor rigidity and responsiveness.Understanding the multifaceted neurochemical regulation of catalepsy enhances the development of safer neuropsychiatric drugs and improves models for extrapyramidal side effects. Future research should focus on integrated neurotransmitter targeting and the development of modulators with minimized cataleptogenic potential.