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  2. Effects of GABAa receptor antagonists on motor behavior in pharmacological Parkinson's disease model in mice

Effects of GABAa receptor antagonists on motor behavior in pharmacological Parkinson's disease model in mice

  • Physiol Rep. 2017 Mar;5(6):e13081. doi: 10.14814/phy2.13081.
Karla De Michelis Mograbi 1 Ana Carolini Ferreira de Castro 2 Jainny Aniely Rocha de Oliveira 2 Patrick Jean Barbosa Sales 2 Luciene Covolan 3 Eliane Aparecida Del Bel 4 Albert Schiaveto de Souza 2
Affiliations

Affiliations

  • 1 Laboratory of Biophysiopharmacology, Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil kamograbi@yahoo.com.br.
  • 2 Laboratory of Biophysiopharmacology, Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil.
  • 3 Laboratory of Neurophysiology, Universidade Federal de São Paulo, Sao Paulo, Brazil.
  • 4 Laboratory of Physiology, Universidade de São Paulo, Sao Paulo, Brazil.
Abstract

The aim of this study was to evaluate the effects of two gamma-amino butyric acid (GABA)a receptor antagonists on motor behavioral tasks in a pharmacological model of Parkinson disease (PD) in rodents. Ninety-six Swiss mice received intraperitoneal injection of Haloperidol (1 mg/kg) to block dopaminergic receptors. GABAa receptors antagonists Bicuculline (1 and 5 mg/kg) and Flumazenil (3 and 6 mg/kg) were used for the assessment of the interaction among these neurotransmitters, in this PD model. The motor behavior of the Animals was evaluated in the catalepsy test (30, 60, and 90 min after drugs application), through open field test (after 60 min) and trough functional gait assessment (after 60 min). Both Bicuculline and Flumazenil were able to partially reverse catalepsy induced by Haloperidol. In the open field test, Haloperidol reduced the number of horizontal and vertical exploration of the Animals, which was not reversed trough application of GABAa antagonists. Furthermore, the functional gait assessment was not sensitive enough to detect motor changes in this animal model of PD. There is an interaction between dopamine and GABA in the basal ganglia and the blocking GABAa receptors may have therapeutic potential in the treatment of PD.

Keywords

GABA; Bicuculline; catalepsy; flumazenil.

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