Abstract
Corticotropin-releasing factor receptor type 1 (CRFR1) plays a major role in the regulation of neuroendocrine and behavioral responses to stress and is considered a key mediator of anxiety behavior. The globus pallidus external (GPe), a main relay center within the basal ganglia that is primarily associated with motor and associative functions, is one of the brain nuclei with the highest levels of CRFR1 expression in the rodent brain. However, the role of CRFR1 in the GPe is yet unknown. In the present study, we used a lentiviral-based system of RNA interference to show that knockdown of CRFR1 mRNA expression in the GPe of adult mice induces a significant increase in anxiety-like behavior, as revealed by the light-dark transfer, open-field, and elevated plus-maze tests. This effect was further confirmed by pharmacological administration of the selective CRFR1 antagonist NBI 30775 (1.75 μg/side) directly into the GPe. In the marble-burying test, blockade of CRFR1 in the GPe increased the percentage of marbles buried and the duration of burying behavior. Additionally, we present evidence suggesting that the enkephalin system is involved in the effect of GPe-CRFR1 on anxiety-like behavior. In contrast to the well established anxiogenic role of CRFR1 in the extended amygdala, our data reveal a novel anxiolytic role for CRFR1 in the GPe.