GABAergic neurotransmission is thought to play an important role in the modulation of the central response to stress. In the present study we evaluate the influence of a brief restraint exposure on GABA-stimulated chloride influx in diverse brain areas presumed to have a major role in the mediation of emotional behaviors following aversive stimulation. A reduced chloride uptake after stress exposure was only observed in frontal cortex and amygdala. Moreover, rats subjected to such stressor performed an anxiogenic behavior when exposed later to the elevated plus-maze. A comparable behavior in the elevated plus-maze was observed between animals that were allowed to chew during the restraint experience and those without any stressful manipulation, suggesting that chewing served as an efficient coping behavioral strategy during such threatening situations. In order to explore if chewing during the restraint experience could suppress the reduction in GABA-stimulated chloride uptake induced by this stressor, rats were allowed or not to chew during restraint and in both cases GABA-stimulated chloride influx was assayed in frontal cortex and amygdala. The finding of this experiment showed that restrained rats that have the possibility to chew exhibited a similar GABA-stimulated chloride uptake in cortical tissue to that shown by control, unstressed rats. Moreover, chewing in response to restraint attenuated the reduction of GABA-stimulated chloride uptake in amygdala, supporting the notion that chewing is an effective coping response to restraint. These experiments suggest that a reduced GABAergic inhibitory control in these areas could be implicated in the emotional sequelae generated by this uncontrollable stressor and that the suppression of this reduction seems to be associated with the occurrence of coping behavioral response to such fear-inducing stimulus.
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Pestic Biochem Physiol
May 2022
Louisiana State University Agricultural Center, Department of Entomology, Baton Rouge, LA 70803, USA. Electronic address:
Nootkatone, a sesquiterpenoid isolated from Alaskan yellow cedar (Cupressus nootkatensis), is known to possess insect repellent and acaricidal properties and has recently been registered for commercial use by the Environmental Protection Agency. Previous studies failed to elucidate the mechanism of action of nootkatone, but we found a molecular overlay of picrotoxinin and nootkatone indicated a high degree of structural and electrostatic similarity. We therefore tested the hypothesis that nootkatone was a GABA-gated chloride channel antagonist, similar to picrotoxinin.
View Article and Find Full Text PDFNeuropsychopharmacology
April 2008
Department of Psychology, The University at Albany-SUNY, Albany, NY 12222, USA.
Although androgen secretion is reduced with aging, and may underlie decrements in cognitive and affective performance, the effects and mechanisms of androgens to mediate these behaviors are not well understood. Testosterone (T), the primary male androgen, is aromatized to estrogen (E(2)), and reduced to dihydrotestosterone (DHT), which is converted to 5alpha-androstane, 3alpha, 17beta-diol (3alpha-diol). To ascertain whether actions of the neuroactive metabolite of T, 3alpha-diol, mediates cognitive and affective behaviors, intact, aged male C57/B6 mice (24 month old) as well as young, intact and gonadectomized (GDX; 12 week old) mice were administered s.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
December 2006
Behavioral Neuroscience, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Studies using mice with point mutations of GABA(A) receptor alpha subunits suggest that the sedative and anxiolytic properties of 1,4-benzodiazepines are mediated, respectively, by GABA(A) receptors bearing the alpha(1) and alpha(2) subunits. This hypothesis predicts that a compound with high efficacy at GABA(A) receptors containing the alpha(1) subunit would produce sedation, whereas an agonist acting at alpha(2) subunit-containing receptors (with low or null efficacy at alpha(1)-containing receptors) would be anxioselective. Electrophysiological studies using recombinant GABA(A) receptors expressed in Xenopus oocytes indicate that maximal potentiation of GABA-stimulated currents by the pyrazolo-[1,5-a]-pyrimidine, DOV 51892, at alpha(1)beta(2)gamma(2S) constructs of the GABA(A) receptor was significantly higher (148%) than diazepam.
View Article and Find Full Text PDFPsychopharmacology (Berl)
June 2006
Department of Psychology, The University at Albany, SUNY, Albany, NY 12222, USA.
Rationale: Aging is associated with reduced secretion of, and down-regulation of receptors for, progesterone (P); yet, P's effects when administered to younger and older animals have not been systematically investigated. Some of P's antianxiety effects may be due to its conversion to 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) and its subsequent actions as a positive modulator at GABAA receptor complexes (GBRs).
Objectives: We investigated whether P administration can decrease anxiety behavior of progestin receptor (PR) knockout (PRKO) or wild-type control mice.
Genes Brain Behav
February 2006
Portland Alcohol Research Center, Department of Veterans Affairs Medical Center, Oregon Health & Science University, Portland, OR 97239, USA.
The neurosteroid allopregnanolone (ALLO) is a potent positive modulator of gamma-aminobutyric acid(A) (GABA(A)) receptors. Earlier work indicates that sensitivity to the anticonvulsant effect of ALLO was enhanced during ethanol (EtOH) withdrawal in rats and in C57BL/6 mice, an inbred strain with mild EtOH withdrawal. In contrast, ALLO sensitivity was reduced during EtOH withdrawal in DBA/2 mice, an inbred strain with severe EtOH withdrawal.
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