Amygdala β-Noradrenergic Receptors Modulate Delayed Downregulation of Dopamine Activity following Restraint

Abstract

Stress, which involves a heightened arousal and excitability, triggers important adaptive responses to maintain homeostasis and prepare a response. In the current studies, we administered a psychological stressor of 2 h acute restraint on rats, and found that 24 h after the cessation of the restraint session, there was a significant decrease in VTA DA neuron population activity and a significant attenuation in amphetamine-induced locomotor activity. Systemic or intra-BLA administration of the β-noradrenergic receptor antagonist, propranolol, reversed the decrease, suggesting that the delayed attenuation of DA neuron firing following a stressor depends on a noradrenaline-mediated mechanism. This alteration in DA activity may adaptively prepare the individual to avoid the stressor, or in the extreme, may be a factor that contributes to pathological changes in behavior or physiological responses.

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

“…Other studies with this chimeric receptor used a 10-Hz (50 ms) stimulation paradigm that resulted in no significant behavioral output in the nucleus accumbens, a region with low β-adrenergic receptor expression (Airan et al, 2009). We know that NE release in the BLA is predicated on inputs from the LC, whose activity contributes to an animal's arousal state (Aston-Jones and Cohen, 2005;Berridge and Waterhouse, 2003;Bouret and Sara, 2005;Chang and Grace, 2013). At rest, the LC is spontaneously active, while acute stress shifts the firing patterns to increased tonic activity (5-8 Hz) or initiates phasic bursting to cause temporally distinct release of NE (Abercrombie and Jacobs, 1987a, b;Galvez et al, 1996;Mana and Grace, 1997;Quirarte et al, 1998).…”

Acute stressor effects on goal-directed action in rats

“…Second, single exposure to an acute stressor not only triggers immediate short-lasting effects but also delayed effects in an hours-to-days range that involve neurochemical and genomic actions of stress mediators (Joels and Baram 2009). For instance, an acute restraint stressor can cause an immediate increase in striatal dopamine release followed by a delayed down-regulation of midbrain dopamine neuron activity 24 h after cessation of restraint (Chang and Grace 2013). Furthermore, multiple stressor exposure could compromise reconsolidation after retrieval of action-outcome contingencies on test day 1 and, in turn, retrieval on test day 2.…”

Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression

“…However, when examined at longer time points following stress or amphetamine withdrawal there is a 50% reduction in tonic DA activity. 54, 55 This compensatory down-regulation following DA system activation is referred to as an opponent process 56, 57 ; that is, when the DA system is acutely activated, there is a subsequent, prolonged compensatory decrease in the responsivity of the DA system. This subsequent DA down-regulation is dependent on the BLA 54, 55 .…”

“…The duration of the stressor impacts the magnitude and duration of the negative affective state associated with its withdrawal 56, 57 . Thus, acute activation of the DA system by amphetamine or stress-induced DA neuron activation is followed by a depression of DA neuron firing 54, 55 . However, if the stressor is presented over a much longer period of time, the consequent depressive-like state is also maintained for an extended period following withdrawal.…”