High fat diet induced-obesity facilitates anxiety-like behaviors due to GABAergic impairment within the dorsomedial hypothalamus in rats.
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2017
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Abstract
Overweight and obesity are conditions associated with an overall range of clinical health consequences,
and they could be involved with the development of neuropsychiatric diseases, such as generalized anxiety
disorder (GAD) and panic disorder (PD). A crucial brain nuclei involved on the physiological functions
and behavioral responses, especially fear, anxiety and panic, is the dorsomedial hypothalamus (DMH).
However, the mechanisms underlying the process whereby the DMH is involved in behavioral changes
in obese rats still remains unclear. The current study further investigates the relation between obesity
and generalized anxiety, by investigating the GABAA sensitivity to pharmacological manipulation within
the DMH in obese rats during anxiety conditions. Male Wistar rats were divided in two experimental
groups: the first was fed a control diet (CD; 11% w/w) and second was fed a high fat diet (HFD; 45%
w/w). Animals were randomly treated with muscimol, a GABAA agonist and bicuculline methiodide (BMI),
a GABAA antagonist. Inhibitory avoidance and escape behaviors were investigated using the Elevated
T-Maze (ETM) apparatus. Our results revealed that the obesity facilitated inhibitory avoidance acquisition,
suggesting a positive relation between obesity and the development of an anxiety-like state. The
injection of muscimol (an anxiolytic drug), within the DMH, increased the inhibitory avoidance latency in
obese animals (featuring an anxiogenic state). Besides, muscimol prolonged the escape latency and controlling
the possible panic-like behavior in these animals. Injection of BMI into the DMH was ineffective
to produce an anxiety-like effect in obese animals opposing the results observed in lean animals. These
findings support the hypotheses that obese animals are susceptible to develop anxiety-like behaviors,
probably through changes in the GABAergic neurotransmission within the DMH.
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NORONHA, S. I. S. R. de et al. High fat diet induced-obesity facilitates anxiety-like behaviors due to GABAergic impairment within the dorsomedial hypothalamus in rats. Behavioural Brain Research, v. 316, p. 38-46, 2017. Disponível em: <http://www.sciencedirect.com/science/article/pii/S0166432816305605?via%3Dihub>. Acesso em: 15 set. 2017.