Abstract
The human insula has been consistently reported to be overactivated in all anxiety disorders, activation which has been suggested to be proportional to the level of anxiety and shown to decrease with effective anxiolytic treatment. Nonetheless, studies evaluating the direct role of the insula in anxiety are lacking. Here, we set out to investigate the role of the rodent insula in anxiety by either inactivating different insular regions via microinjections of glutamatergic AMPA receptor antagonist CNQX or activating them by microinjection of GABA receptor antagonist bicuculline in rats, before measuring anxiety-like behavior using the elevated plus maze. Inactivation of caudal and medial insular regions induced anxiogenic effects, while their activation induced anxiolytic effects. In contrast, inactivation of more rostral areas induced anxiolytic effects and their activation, anxiogenic effects. These results suggest that the insula in the rat has a role in the modulation of anxiety-like behavior in rats, showing regional differences; rostral regions have an anxiogenic role, while medial and caudal regions have an anxiolytic role, with a transition area around bregma +0.5. The present study suggests that the insula has a direct role in anxiety.
Highlights
Anxiety may be defined as an intensified fear or avoidance in response to objects or situations in the absence of true danger (Shin and Liberzon, 2010), and may be operationally defined as an emotional response to potential unidentified threats, being characterized by sustained arousal, vigilance, worry and apprehension that results in specific patterns of defensive behaviors and concomitant autonomic responses (Tovote et al, 2015)
It has been suggested that the anterior insula contributes to the perception of interoceptive sensations associated to danger or threat, possibly playing a crucial role in anxiety (Paulus and Stein, 2006)
We used the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist CNQX to study the role of insular cortex (IC) in anxiety and to address whether functional differences could be observed along the rostro-caudal axis of the IC by inactivating the IC in different regions along its rostrocaudal axis
Summary
Anxiety may be defined as an intensified fear or avoidance in response to objects or situations in the absence of true danger (Shin and Liberzon, 2010), and may be operationally defined as an emotional response to potential unidentified threats, being characterized by sustained arousal, vigilance, worry and apprehension that results in specific patterns of defensive behaviors and concomitant autonomic responses (Tovote et al, 2015) It is a normal physiological response commonly found after or in anticipation of stressful experiences, but can appear frequently as a symptom in patients suffering from neurological and psychiatric disorders, as well as in chronic disease (Nagai et al, 2007; Brooks and Stein, 2015). Despite the high prevalence of anxiety, the neurobiological basis of anxiety is only beginning to be unveiled
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