Distinct Amygdalar AMPAergic/GABAergic Mechanisms Promote Anxiolitic-Like Effects in an Unpredictable Stress Model of the Hamster

Abstract

Studies have pointed to both α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) antagonists and GABA(A) receptor (GABA(A)R) agonists as potent antistress agents. In this work, separate subchronic injections of the AMPAR antagonist, 6-ciano-7-nitroquinoxaline-2,3-dione (CNQX), and α1 GABA(A)R subunit agonist (Zol) within the central amygdala nucleus modified the elevated plus maze performances of hamsters exposed randomly to one of the following stressful conditions: food/water deprivation, forced swimming test, and permanence in cold room. Indeed, stressed hamsters treated with CNQX or Zol displayed a very great (p < 0.001) increase of entrance plus a moderate (p < 0.05) time spent into open arms, respectively. At the cellular level, Zol-treated animals supplied a moderately evident argyrophilic reaction (indicative of neurodegeneration) in the hippocampus while it was absent in the hypothalamus. Interestingly, this reaction was significantly reduced by CNQX supporting its preferential protective role. Furthermore, both agents were responsible for a mixed expression pattern of GluR1 and GluR2 mRNA levels in which Zol overall upregulated GluR1 mRNAs, while they were downregulated by CNQX in the hippocampal oriens-pyramidalis layer and in layer III of the cerebral cortex. These findings support the amygdalar AMPAergic protective response against anxiety states in chronically stressed hamsters, which may constitute useful therapeutic strategies for panic-related mood disorders.

Stress in Regulation of GABA Amygdala System and Relevance to Neuropsychiatric Diseases

“…Some animal experiments have indicated that administration of GABA receptor agonists or antagonists into the amygdala can influence the concentration of GABA ( Sanders and Shekhar, 1995 ; Barbalho et al, 2009 ). These have included GABAergic agonists such as benzodiazepines ( Sigel and Lüscher, 2011 ), Zol ( Alò et al, 2015 ), muscimol ( Jasnow and Huhman, 2001 ; Liu et al, 2009 ), diazepam, and abecarnil ( Eva et al, 2004 ). GABAergic antagonists have included baclofen ( Gorsane et al, 2012 ), bicuculline ( Liu et al, 2009 ), and FG-7124 ( Eva et al, 2004 ; Lukkes et al, 2012 ).…”

“…GABAergic antagonists have included baclofen ( Gorsane et al, 2012 ), bicuculline ( Liu et al, 2009 ), and FG-7124 ( Eva et al, 2004 ; Lukkes et al, 2012 ). Benzodiazepines, Zol, diazepam, and abecarnil bind the subunits of GABA A receptors, and this binding increases the probability of ion channel opening in the presence of GABA ( Eva et al, 2004 ; Alò et al, 2015 ; Fast and McGann, 2017 ). On the other hand, baclofen competes with GABA for the same sites on GABA B receptors in the amygdala.…”

Structural Features and Potent Antidepressant Effects of Total Sterols and β-sitosterol Extracted from Sargassum horneri

“…In addition, a number of evidences confirm the active role played by the glutamate ( l -Glu) neuroreceptor system on the pharmacological therapeutic mechanisms of antidepressants [ 9 ]. N -methyl- d -aspartate receptors (NMDARs) or α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid l -Glu receptors (AMPARs) are major targets of the various chronic depressive disorders [ 10 , 11 ].…”

Genistein Modifies Hamster Behavior and Expression of Inflammatory Factors following Subchronic Unpredictable Mild Stress

“…Brain coronal sections (30 µm) were selected at an interval of 240 µm for ACS procedures in which an exposition period (25 min) to neutral red for the different brain sections was adapted for our animal model [14]. Briefly, sections were rinsed with distilled water, placed into dishes containing a pre-impregnating solution heated in a microwave oven at 45–50°C for 50 min, and cooled at room temperature for 3 h. Sections were then rinsed in distilled water, and after a quick rinse in acetone they were placed in an impregnating AgNO 3 solution for 50 min, followed by a 25-min fixation in a reducer solution (formalin, citric acid monohydrate, ethanol, distilled water) at a temperature range of 32–35°C.…”

“…This rodent model was chosen on the basis of its notable ability to tolerate chronic stressful conditions [12]. Specific tests were applied to evaluate different stress-associated behaviors: the elevated plus maze (EPM) test, used for evaluating psychomotor performances in hamsters [13, 14], and the hole board (HB) test, used for exploratory behaviors in rodents [15]; both tests are considered to be valid for assessing anxiolytic effects. Contextually, forced swim test (FST) was also applied, since it results to be a valuable approach for measuring antidepressant-like effects together with desperation states [16].…”