Expression of chimeric estrogen-glucocorticoid-receptor in the amygdala reduces anxiety.
The basolateral amygdala is critical for generating anxiety, and exposure to glucocorticoids induces anxiety. The demonstrated ability of glucocorticoids to cause dendritic expansion and increase excitability in the amygdala could help mediate the behavioral effects of glucocorticoids, and thus may be important therapeutic target for anxiety. In contrast, estrogen has the opposite effects of glucocorticoids in many domains. In this study, we employed a gene therapeutic approach to reduce anxiety and dendritic arborization of amygdaloid neurons of adult male Wistar rats. We used a herpes simplex viral vector to express a chimeric steroid receptor ("ERGR") which binds glucocorticoids yet transduces their actions into estrogenic effects. When expressed in the basolateral amygdala (BLA), ERGR reduced anxiety, as tested on elevated plus-maze and open field, without affecting conditioned fear, another amygdala-dependent behavior. Moreover, ERGR also blocked glucocorticoid-induced dendritic expansion of BLA neurons. Thus ERGR expression in the BLA provides a potential therapeutic against anxiety disorders.
Mitra
Rupshi
R
Department of Biology, Stanford University, Stanford, CA 94305, USA.
Sapolsky
Robert M
RM
D000679:Amygdala / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001008:Anxiety Disorders / Q000139:chemically induced / Q000628:therapy*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005938:Glucocorticoids / Q000494:pharmacology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics*
D047628:Estrogen Receptor alpha; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins