Does amygdaloid corticotropin-releasing hormone (CRH) mediate anxiety-like behaviors? Dissociation of anxiogenic effects and CRH release

Document Type



Brain and Mind Institute


The brain corticotropin-releasing hormone (CRH) circuits are activated by stressful stimuli, contributing to behavioral and emotionalresponses. The present study assessed anxiety-like responses andin vivoneurochemical alterations at the central nucleus of theamygdala (CeA) evoked by exposure to an unfamiliar (anxiogenic) environment. Also, the impact of anxiolytic treatments and thosethat affect CRH were assessed in this paradigm. Novel environment (new cage) markedly suppressed ingestion of a palatable snack.This effect was dose-dependently antagonized by diazepam and was utilized as an index of anxiety in the rodent. Although exposureto a novel environment also stimulated thein vivorelease of CRH and glutamate at the CeA, various CRH antagonists (e.g.ah-CRH,Ca-MeCRH, CP-154,526, antisauvagine-30, preproTRH178-199) did not attenuate the stressor-elicited behavioral suppression,although Ca-MeCRH was found to attenuate the freezing response elicited by contextual stimuli that were associated with previouslyadministered footshock. Moreover, central infusion of CRH failed to suppress snack consumption in the home cage. Althoughdiazepam had potent anxiolytic effects in this paradigm, this treatment did not prevent the stressor-associated release of CRH andglutamate at the CeA. Thus, while neural circuits involving CRH and⁄or glutamatergic receptors at the CeA may be activated by anunfamiliar environment, the data challenge the view that activation of these receptors is necessary for the expression of anxiety-likebehavioral responses. Rather than provoking anxiety, these systems might serve to draw attention to events or cues of biologicalsignificance, including those posing a threat to survival.


This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

European Journal of Neuroscience