Roles of corticotropin-releasing factor signaling in the lateral habenula in anxiety-like and alcohol drinking behaviors in male rats.
Publication/Presentation Date
11-1-2021
Abstract
Corticotropin-releasing factor (CRF) signaling in the mesocorticolimbic system is known to modulate anxiety-like behavior and alcohol consumption, behaviors that also have been associated with the hyper-glutamatergic state of the lateral habenula (LHb) neurons in rats. However, the role of CRF signaling in the LHb on the glutamate transmission, anxiety-like behaviors and alcohol consumption is unknown. Here, we used male rats that had been consuming alcohol for three months to address this gap in the literature. First, using electrophysiological techniques, we evaluated CRF's effects on the glutamate transmission in LHb neurons in brain slices. CRF facilitated glutamate transmission. The facilitation was greater in neurons of alcohol-withdrawing rats than in those of naïve rats. The facilitation was mimicked by the activation of CRF receptor 1 (CRF1R) but attenuated by the activation of CRF receptor 2 (CRF2R). This facilitation was mediated by upregulating CRF1R-protein kinase A signaling. Conversely, protein kinase C blockade attenuated CRF's facilitation in neurons of naïve rats but promoted it in neurons of alcohol-withdrawing rats. Next, using site-direct pharmacology, we evaluated the role of CRF signaling in the LHb on anxiety-like behaviors and alcohol consumption. Intra-LHb inhibition of CRF1R or activation of CRF2R ameliorated the anxiety-like behaviors in alcohol-withdrawing rats and reduced their alcohol intake when drinking was resumed. These observations provide the first direct behavioral pharmacological and cellular evidence that CRF signaling in the LHb modulates glutamate transmission, anxiety-like behaviors and alcohol consumption, and that adaptation occurs in CRF signaling in the LHb after chronic alcohol consumption.
Volume
15
First Page
100395
Last Page
100395
ISSN
2352-2895
Published In/Presented At
Zuo, W., Zuo, Q., Wu, L., Mei, Q., Shah, M., Zheng, J., Li, D., Xu, Y., & Ye, J. H. (2021). Roles of corticotropin-releasing factor signaling in the lateral habenula in anxiety-like and alcohol drinking behaviors in male rats. Neurobiology of stress, 15, 100395. https://doi.org/10.1016/j.ynstr.2021.100395
Disciplines
Anesthesiology | Medicine and Health Sciences
PubMedID
34568522
Department(s)
Department of Anesthesiology
Document Type
Article