Editors' ChoiceNeuroscience

Binge drinking for stress relief

See allHide authors and affiliations

Science Signaling  07 Apr 2015:
Vol. 8, Issue 371, pp. ec81
DOI: 10.1126/scisignal.aab2788

Binge drinking is a common form of alcohol abuse that is often perceived as a way to relieve stress. Binge drinking may alter signaling in the neuronal circuits that regulate reward-seeking behavior and sensitivity to stress. The anti-stress neuropeptide NPY suppresses anxiety, whereas the stress-related hormone corticotropin-releasing factor [CRF, also known as corticotropin-releasing hormone (CRH)] increases anxiety and encourages ethanol drinking in mice. Pleil et al. found that NPY signaling induced inhibitory postsynaptic currents in CRF-containing neurons in the hypothalamic-pituitary-adrenal axis of the brain, which is involved in reward and anxiety behaviors, and that binge drinking increased this effect by increasing NPY receptor abundance in CRF neurons. Infusion of an agonist to the NPY receptor Y1R into the bed nucleus of the stria terminalis (BNST, a part of the hypothalamic-pituitary-adrenal axis), but not the adjacent dorsal striatum, suppressed binge alcohol drinking in mice, whereas infusion of a Y1R antagonist into the BNST increased alcohol consumption. In BNST slices from mice or monkeys that had chronic ethanol consumption, bath administration of a Y1R agonist increased the frequency of miniature inhibitory postsynaptic currents (mIPSCs). In reporter mice, this increased mIPSC frequency occurred in CRF-positive neurons. Bathing slices or injecting postsynaptic neurons in the slices with selective inhibitors of the G protein heterotrimer Gi, protein kinase A (PKA), or receptor trafficking and then monitoring the mIPSC frequency in response to application of NPY or the Y1R agonist revealed that Y1R is a postsynaptic Gi-coupled receptor in the BNST that increases the abundance of postsynaptic γ-aminobutyric acid (GABA)A receptors at the cell surface by inhibiting PKA activity. Chemogenetic (viral and drug-induced) activation of Gi signaling in BNST CRF neurons suppressed binge drinking in mice, whereas activation of Gs signaling and hence PKA signaling in CRF neurons promoted binge drinking. Analysis of the effect of the Y1R agonist given at different times in the day suggested that ethanol alters circadian control of Y1R signaling. Mice that binge drank had greater Y1R abundance and activity in postsynaptic CRF neurons during their active phase. Allthough NPY abundance increased only transiently after each episode of binge drinking, Y1R protein abundance and activity (as measured by increased mIPSC frequency) increased after several cycles of binge drinking and persisted for days. Thus, chronic alcohol use appeared to produce an enduring increase in sensitivity of the NPY-Y1R signaling axis in the BNST, which may explain why binge drinking is perceived as a stress reliever.

K. E. Pleil, J. A. Rinker, E. G. Lowery-Gionta, C. M. Mazzone, N. M. McCall, A. M. Kendra, D. P. Olson, B. B. Lowell, K. A. Grant, T. E. Thiele, T. L. Kash, NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking. Nat. Neurosci. 18, 545–552 (2015). [PubMed]

Stay Connected to Science Signaling