title: High fat diet induced-obesity facilitates anxiety-like behaviors due to GABAergic impairment within the dorsomedial hypothalamus in rats.
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 GABAAsensitivity 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 GABAAagonist and bicuculline methiodide (BMI), a GABAAantagonist. 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.
authors: Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Ouro Preto, MG, Brazil.
authors: Sylvana Rendeiro
authors: SR
authors: de Noronha
authors: Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Ouro Preto, MG, Brazil.
authors: Glenda Viggiano
authors: GV
authors: Campos
authors: Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Ouro Preto, MG, Brazil.
authors: Aline Rezende
authors: AR
authors: Abreu
authors: Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Ouro Preto, MG, Brazil.
authors: Aline Arlindo
authors: AA
authors: de Souza
authors: Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Ouro Preto, MG, Brazil.
authors: Deoclécio A
authors: DA
authors: Chianca
authors: Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Ouro Preto, MG, Brazil. Electronic address: rodrigo.menezes@iceb.ufop.br.
authors: Rodrigo C
authors: RC
authors: de Menezes
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology*; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D059305:Diet, High-Fat / Q000009:adverse effects*; D004302:Dorsomedial Hypothalamic Nucleus / Q000378:metabolism*; D004924:Escape Reaction / Q000187:drug effects; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology / Q000627:therapeutic use; D009765:Obesity / Q000150:complications / Q000209:etiology* / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D009118:Muscimol; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline
keywords: Anxiety; Dorsomedial hypothalamus; GABA; High-fat diet; Obesity