The insula mediates the effects of glucocorticoids in anxiety.

Increased activity in the insula has been consistently reported to be associated with anxiety and anxiety-related disorders. However, little is known on how the insula regulates anxiety. The present study aims at determining the role of the insula on the effects of glucocorticoids in anxiety. A combination of pharmacological manipulations, including blockade of adrenal GC synthesis by metyrapone and intra-insular microinjections of corticosterone, corticosterone-BSA, mineralocorticoid receptor (MR) antagonist spironolactone and glucocorticoid receptor (GR) antagonist mifepristone, were used to assess the short-term (5 min) effects of intra-insular corticosterone in two anxiety-like behaviors in male Sprague-Dawley rats. The elevated plus maze (EPM) and Novelty Suppressed Feeding (hyponeophagia) were utilized. We found that corticosterone in the insula is sufficient to prevent the anxiolytic effects corticosterone synthesis blockade in anxiety, and that intra-insular corticosterone has anxiolytic or anxiogenic effects depending on the amount of corticosterone microinjected and the arousal associated to the test, without affecting the HPA axis. Glucocorticoid anxiolytic effects in the insula are mediated by MRs, while its anxiogenic effects are dependent on a mifepristone-sensitive membrane-bound mechanism. Anxiety appears to be modulated at the insula through a competition between fast MR-dependent anxiolytic and membrane-associated anxiogenic signaling pathways that orchestrate the behavioral response to stress and determines the resulting level of anxiety.

The insula modulates arousal-induced reluctance to try novel tastes through adrenergic transmission in the rat.

Reluctance to try novel tastes (neophobia) can be exacerbated in arousing situations, such as when children are under social stress or in rodents, when the new taste is presented in a high arousal context (HA) compared to a low arousal context (LA). The present study aimed at determining whether adrenergic transmission at the Insula regulates the reluctance to try novel tastes induced by arousing contexts. To this end, a combination of systemic and intra-insular manipulations of adrenergic activity was performed before the novel taste (saccharin 0.1%) was presented either in LA or HA contexts in rats. Our results show that systemic adrenergic activity modulates reluctance to try novel tastes. Moreover, intra-insular microinjections of propranolol or norepinephrine (NE) were found to modulate the effects of arousing contexts on reluctance to try novel tastes. Finally, intra-insular propranolol blocked epinephrine-induced increased reluctance, while intra-insular NE blocked oral propranolol-induced decreases in reluctance and increased the reluctance to try novel tastes presented in low arousing contexts. In conclusion, our results suggest that the insula is a critical site for regulating the effects of arousal in the reluctance to try novel tastes via the adrenergic system.