Noradrenergic enhancement of amygdala responses to fear

Abstract

Multiple lines of evidence implicate the basolateral amygdala (BLA) and the noradrenergic (norepinephrine, NE) system in responding to stressful stimuli such as fear signals, suggesting hyperfunction of both in the development of stress-related pathologies including anxiety disorders. However, no causative link between elevated NE neurotransmission and BLA hyperresponsiveness to fear signals has been established to date in humans. To determine whether or not increased noradrenergic tone enhances BLA responses to fear signals, we used functional magnetic resonance imaging (fMRI) and a strategy of pharmacologically potentiating NE neurotransmission in healthy volunteers. 18 subjects were scanned two times on a facial emotion paradigm and given either a single-dose placebo or 4 mg of the selective NE reuptake inhibitor reboxetine 2 h prior to an fMRI session. We found that reboxetine induced an amygdala response bias towards fear signals that did not exist at placebo baseline. This pharmacological effect was probabilistically mapped to the BLA. Extrapolation of our data to conditions of traumatic stress suggests that disinhibited endogenous NE signaling could serve as a crucial etiological contributor to post-traumatic stress disorder (PTSD) by eliciting exaggerated BLA responses to fear signals.

Serotonergic and Noradrenergic Modulation of Emotion Processing by Single Dose Antidepressants

“…During a categorization task with self-referential emotional words during fMRI, reboxetine induced changes in a frontoparietal cortical network (Miskowiak et al, 2007). The other studies focused on the amygdala during the perception of emotional facial movies (Onur et al, 2009, Kukolja et al, 2008, the former reporting additionally increased activations in frontal, cingular, and occipital brain regions.…”

Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy) in anxiety-like responses in mice

“…Indeed, we have already reported that MDMA (10 mg/kg) increased hypothalamic noradrenergic activity (3). Limbic brain areas, such as hypothalamus, amygdala and hippocampus, exhibit rapid and large increases in noradrenaline turnover in anxiogenic situations (32,34). The mesolimbic dopaminergic system has already been related to anxiety-like responses (35).…”

Estudo de ressonância magnética funcional das mudanças da atividade cerebral durante recordações afetivas autobiográficas decorrentes da administração prolongada de clomipramina a sujeitos saudáveis

“…This effect appears to be independent of the clinical (therapeutic) action, because it also occurs in healthy individuals. [8][9][10]12,48,49 The absence of differences in demographic variables and clomipramine doses between the two groups, whose components were free for personal or family history of psychiatric disorders, indicate that the distinct mood-related and brain activity changes detected in the responder subjects were not due to pharmacokinetic or subclinical factors. Rather, they may conceivably be related to genetic variations in patterns of drug response or 5-HT turnover.…”