Corticosterone regulates both naturally occurring and cocaine-induced dopamine signaling by selectively decreasing dopamine uptake.
Stressful and aversive events promote maladaptive reward-seeking behaviors such as drug addiction by acting, in part, on the mesolimbic dopamine system. Using animal models, data from our laboratory and others show that stress and cocaine can interact to produce a synergistic effect on reward circuitry. This effect is also observed when the stress hormone corticosterone is administered directly into the nucleus accumbens (NAc), indicating that glucocorticoids act locally in dopamine terminal regions to enhance cocaine's effects on dopamine signaling. However, prior studies in behaving animals have not provided mechanistic insight. Using fast-scan cyclic voltammetry, we examined the effect of systemic corticosterone on spontaneous dopamine release events (transients) in the NAc core and shell in behaving rats. A physiologically relevant systemic injection of corticosterone (2 mg/kg i.p.) induced an increase in dopamine transient amplitude and duration (both voltammetric measures sensitive to decreases in dopamine clearance), but had no effect on the frequency of transient release events. This effect was compounded by cocaine (2.5 mg/kg i.p.). However, a second experiment indicated that the same injection of corticosterone had no detectable effect on the dopaminergic encoding of a palatable natural reward (saccharin). Taken together, these results suggest that corticosterone interferes with naturally occurring dopamine uptake locally, and this effect is a critical determinant of dopamine concentration specifically in situations in which the dopamine transporter is pharmacologically blocked by cocaine.
['Wheeler|Daniel S|DS|', 'Ebben|Amanda L|AL|', 'Kurtoglu|Beliz|B|', 'Lovell|Marissa E|ME|', 'Bohn|Austin T|AT|', 'Jasek|Isabella A|IA|', 'Baker|David A|DA|', 'Mantsch|John R|JR|', 'Gasser|Paul J|PJ|', 'Wheeler|Robert A|RA|http://orcid.org/0000-0002-0180-7637']
D000818:Animals D003042:Cocaine D003345:Corticosterone D004298:Dopamine D018765:Dopamine Uptake Inhibitors D008297:Male D009714:Nucleus Accumbens D017207:Rats, Sprague-Dawley D012201:Reward D015398:Signal Transduction
corticosterone dopamine stress cocaine voltammetry