Evaluating the role of α2A-adrenergic receptors in neuronal activity changes following stress-induced reinstatement of cocaine-seeking behaviors
Drug use disorders (DUD) are chronic and debilitating conditions which effect millions of Americans. The rate of relapse in recovering DUD patients is high and dependent on many different factors. Stress and anxiety are cited as major, ubiquitous, precipitating factors in relapse. Because the neural circuitries underlying relapse and stress are mediated by the norepinephrine system; for several decades, this system has been a target of pharmacological treatments aimed at decreasing stress and relapse. Evidence suggests that brain regions involved in prolonged stress and fear are under direct control of the noradrenergic system via alpha and beta adrenergic receptors (ARs). Activation of α2A-ARs can prevent stress-induced relapse by inhibiting neuronal activity whereas ligation of β-ARs promotes relapse by increasing neuronal activity. Where in the brain α2A-mediated modulation of stress-induced relapse occurs remains unknown. The mechanisms by which neuronal activation promotes stress-induced relapse also remain to be discovered. We therefore set out to determine the effects of genetic manipulation of α2A-ARs on the marker of neuronal activation, and immediate early gene, c-Fos, in brain regions implicated in stress-induced relapse. In order to address this question, we are employing a combination of behavioral neuropharmacology, in-situ hybridization and confocal microscopy in a mouse model of stress-induced relapse. In mice lacking the inhibitory α2A-AR, we expect to find higher levels of c-Fos expression in stress-sensitive regions. The current study will help inform the development of new clinical treatments for ameliorating the effects of stress on recovering patients by identifying roles of the α2A-ARs.