GABAA ρ receptor mechanisms in the rat amygdala and its role in the modulation of fear and anxiety

Abstract

It is suggested that GABA(A) ρ receptors may have a role in the amygdaloid modulation of fear and anxiety.

GABAA Receptors Containing ρ1 Subunits Contribute to In Vivo Effects of Ethanol in Mice

“…Detailed evidence for GABA A ρ receptor expression and functional responses in the CNS can be found in the review by Martinez-Delgado et al, 2010, where these receptors have been associated with mediating neuronal excitability in the superior colliculus, phasic inhibition at interneuron Purkinje-cell synapses, and protection against neurotoxicity in hippocampal cultures [43]. GABA A ρ receptors may play a role in fear, anxiety, learning, and memory since ρ1/ρ2 antagonists enhance anxiety-related behavior in the elevated plus maze and enhance learning and memory in the Morris water maze [50], [51]. In addition to our in vivo data, several lines of evidence link these receptors to ethanol action: 1) ethanol inhibits the function of both ρ1 and ρ2 GABA A receptors similarly; 2) there is genetic correlation of ρ1 mRNA expression with ethanol consumption and motor activation in NAc in BxD RI mice (r = 0.77, 10% ethanol preference in two-bottle choice test and r = −0.48, ethanol-induced motor response, distance traveled 0–5 minute time interval, from genenetwork.org); 3) family-based association analyses demonstrate that single nucleotide polymorphisms in both human genes ( GABRR1 and GABRR2 ) were significantly associated with alcohol dependence, and the association is strongest when the analysis is focused upon those with earlier onset of alcohol dependence [18].…”

Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics

“…For another, several lines of evidence link r GABA A receptors to physiologically relevant actions of ethanol. In addition to retina, r GABA A subunits have been found in many brain regions, and specific antagonists to r GABA A receptors enhance anxiety in the elevated plus maze, as well as learning and memory in the Morris water maze (Chebib et al, 2009;Flores-Gracia et al, 2010). Furthermore, r1 GABA A receptor expression in the nucleus accumbens is correlated with ethanol consumption and motor activation in mice (r = 0.77, ethanol preference in two-bottle choice test, 10% ethanol; r = 20.48, ethanol-induced motor response, distance traveled, 0-to 5-minute time interval; from genenetwork.org).…”

Expression of GABAρ receptors in the neostriatum: localization in aspiny, medium spiny neurons and GFAP‐positive cells

“…These receptors have been located in the amygdala (Delaney and Sah 1999; Fujimura et al. 2005; Flores‐Gracia et al. 2010; Rosas‐Arellano et al.…”

“…Despite the accumulated knowledge about GABAq receptors their specific function in the central nervous system remains largely unknown. These receptors have been located in the amygdala (Delaney and Sah 1999;Fujimura et al 2005;Flores-Gracia et al 2010;Rosas-Arellano et al 2011), in the mitral layer of the olfactory bulb (Chen et al 2007), Purkinje neurons of cerebellum (Drew and Johnston 1992;Albrecht et al 1997;Boue-Grabot et al 1998;Rozzo et al 2002;Harvey et al 2006;Mejía et al 2008;); in the gray layer of the superior colliculus (Wegelius et al 1998;Pasternack et al 1999;Schmidt et al 2001;Frazao et al 2007;Born and Schmidt 2008;Wahle and Schmidt 2009), in the oval and pyramidal neurons of layers II-VI of the visual cortex (Wegelius et al 1998;Wahle and Schmidt 2009;Rosas-Arellano et al 2011); in the corpus callosum (López-Chávez et al 2005); in brainstem and spinal cord (Johnston et al 1975;Wegelius et al 1998;Rozzo et al 2002;Zheng et al 2003;Milligan et al 2004;López-Chávez et al 2005;Frazao et al 2007;Rosas-Arellano et al 2007). In addition, several reports indicate that the pyramidal neurons of CA1-CA3 areas, dentate gyrus, and subiculum of the hippocampus express GABAq receptors (Strata and Cherubini 1994;Cherubini et al 1998;Wegelius et al 1998;Didelon et al 2002;…”