Noradrenergic modulation of stress induced catecholamine release: Opposing influence of FG7142 and yohimbine

Abstract

ABSTRACTBackground: Life stress modulates decision making, particularly in the face of risk, in some cases prompting vulnerable populations to make suboptimal, life-altering choices. In the brain, stress is known to alter the extracellular release of catecholamines in structures such as basolateral amygdala (BLA) and nucleus accumbens (NAc), but the relationship between catecholamines and decision-making behavior under stress has not been systemically explored.Methods:We developed an operant touchscreen decision-making task for rats comprising elements of loss aversion and risk seeking behavior. Rats were first injected systemically with an adrenergic α2A-receptor agonist (guanfacine) and antagonist (yohimbine), as well as a partial inverse GABAA agonist, FG 7142, known to induce anxiety and stress related physiological responses in a variety of species, including humans. We then used fiber photometry to monitor NE in the basolateral amygdala (BLA), and DA activity in the nucleus accumbens (NAc) while animals engaged in decision-making and following systemic injections of FG 7142 and yohimbine.Results:Neither yohimbine nor guanfacine had any impact on decision making strategy but altered motivational state with yohimbine making the animal almost insensitive to the reward outcome. The pharmacological induction of stress with FG 7142 biased the rats’ decisions towards safety, but this bias shifted toward risk when co-treated with yohimbine. In the BLA and NAc, the FG 7142 altered catecholamine release, with systemic yohimbine producing opposing effects on NE and DA release.Conclusions: Stress induced changes in catecholamine release in the BLA and NAc can directly influence loss sensitivity, decisions and motivation, which can be modulated by the α2A adrenoreceptor antagonist, yohimbine.