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The Chronic Oral Administration of Clobenzorex or Amphetamine Decreases Motor Behavior and Induces Glial Activation in the Striatum Without Dopaminergic Degeneration

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Abstract

Described as amphetamine-like due to their structural and stimulant similarities, clobenzorex is one of the five most-commonly used drugs in Mexico for the treatment of obesity. Various studies have shown that amphetamines induce dopaminergic neurotoxicity and neuroinflammation in the striatum, symptoms which are associated with motor damage. For this reason, the present study aimed to evaluate the effect of chronic clobenzorex administration on motor behaviors, TH immunoreactivity, gliosis, and the neurodegenerative process in the striatum and substantia nigra pars compacta (SNpc). The present research was conducted on three experimental groups of male Wistar rats: the vehicle group, the amphetamine group (2 mg/kg), and the clobenzorex group (30 mg/kg). All groups were subject to oral administration every 24 h for 31 days. Motor activity and motor coordination were evaluated in the open field test and the beam walking test, respectively. The animals were euthanized after the last day of treatment to enable the extraction of their brains for the evaluation of tyrosine hydroxylase (TH) levels, the immunoreactivity of the glial cells, and the neurodegeneration of both the striatum and SNpc via amino-cupric-silver stain. The results obtained show that amphetamine and clobenzorex administration decrease motor activity and motor coordination in the beam walking test and cause increased gliosis in the striatum, while no significant changes were observed in terms of immunoreactivity to TH and neurodegeneration in both the striatum and SNpc. These results suggest that the chronic administration of clobenzorex may decrease motor function in a manner similar to amphetamine, via the neuroadaptive and non-neurotoxic changes caused to the striatum under this administration scheme.

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Acknowledgements

Our thanks to Dr. Victor Alemán, CINVESTAV (IPN, Mexico City), for the donation of the drug (+) amphetamine hydrochloride. Clobenzorex hydrochloride was provided by the Claude Bernard bioterium at the BUAP. Thanks to Benjamin Stewart (English language native and academic proof-reader) for editing the English language text.

Funding

This work was supported by a grant from extraordinary support VIEP-BUAP-2020 given to Patricio-Martínez A.

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  1. Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico

    Grego David Apóstol del Rosal, Ilhuicamina Daniel Limón & Aleidy Patricio-Martínez

  2. Laboratorio de Neuroquímica, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico

    Isabel Martínez

  3. Facultad de Ciencias Biológicas, Benemérita Universidad Autónoma de Puebla, Blvd. Valsequillo y Av. San Claudio Edificio BIO-1 C.U. Col. Jardines de San Manuel A.P, 72570, Puebla, Mexico

    Aleidy Patricio-Martínez

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Apóstol del Rosal, G.D., Limón, I.D., Martínez, I. et al. The Chronic Oral Administration of Clobenzorex or Amphetamine Decreases Motor Behavior and Induces Glial Activation in the Striatum Without Dopaminergic Degeneration. Neurotox Res 39, 1405–1417 (2021). https://doi.org/10.1007/s12640-021-00395-1

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