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. 2017 Mar;5(6):e13081.
doi: 10.14814/phy2.13081.

Effects of GABAa Receptor Antagonists on Motor Behavior in Pharmacological Parkinson's Disease Model in Mice

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Free PMC article

Effects of GABAa Receptor Antagonists on Motor Behavior in Pharmacological Parkinson's Disease Model in Mice

Karla De Michelis Mograbi et al. Physiol Rep. .
Free PMC article

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.

Figures

Figure 1
Figure 1
Graphic related to catalepsy time in each experimental group, at each time of the catalepsy test, in Experiment I. *Significant difference from Haloperidol + Saline group (Student–Newman–Keuls post hoc test, P < 0.05).
Figure 2
Figure 2
Graphic related to horizontal and vertical exploration at open field test in each experimental group – Experiment I. *Significant difference from groups that receive saline as the first drug (Student–Newman–Keuls, P < 0.05).
Figure 3
Figure 3
Graphic related to catalepsy time in each experimental group, at each time of the catalepsy test, in Experiment II. *Significant difference from Haloperidol + Saline group (Student–Newman–Keuls post hoc test, P < 0.05).
Figure 4
Figure 4
Graphic related to horizontal and vertical exploration in open field test at each experimental group – Experiment II. *Significant difference from groups that receive saline as the first drug (Student–Newman–Keuls, P < 0.05).

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