Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking

Abstract

Binge alcohol drinking is a tremendous public health problem because it leads to the development of numerous pathologies, including alcohol abuse and anxiety. It is thought to do so by hijacking brain systems that regulate stress and reward, including neuropeptide Y (NPY) and corticotropin-releasing factor (CRF). The central actions of NPY and CRF have opposing functions in the regulation of emotional and reward-seeking behaviors; thus, dysfunctional interactions between these peptidergic systems could be involved in the development of these pathologies. We used converging physiological, pharmacological and chemogenetic approaches to identify a precise neural mechanism in the bed nucleus of the stria terminalis (BNST), a limbic brain region involved in pathological reward and anxiety behaviors, underlying the interactions between NPY and CRF in the regulation of binge alcohol drinking in both mice and monkeys. We found that NPY Y1 receptor (Y1R) activation in the BNST suppressed binge alcohol drinking by enhancing inhibitory synaptic transmission specifically in CRF neurons via a previously unknown Gi-mediated, PKA-dependent postsynaptic mechanism. Furthermore, chronic alcohol drinking led to persistent alterations in Y1R function in the BNST of both mice and monkeys, highlighting the enduring, conserved nature of this effect across mammalian species. Together, these data provide both a cellular locus and signaling framework for the development of new therapeutics for treatment of neuropsychiatric diseases, including alcohol use disorders.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Activation of Gi-coupled Y1R in the BNST reduces binge ethanol drinking and enhances GABAergic transmission via a PKA-dependent, postsynaptic insertion of GABAA receptors.
Figure 2: Circadian regulation of receptor-specific NPY modulation of GABAergic transmission in the BNST.
Figure 3: Chronic binge alcohol drinking alters receptor-specific NPY modulation of GABAergic transmission in the BNST of mice and monkeys.
Figure 4: Y1R-mediated effects on inhibition in the BNST are specific to CRF neurons.
Figure 5: Direct in vivo chemogenetic activation of Gi signaling in BNST CRF neurons recapitulates, whereas chemogenetic activation of Gs signaling blocks the effect of Y1R activation on binge ethanol consumption.

Similar content being viewed by others

References

  1. Koob, G.F. A role for brain stress systems in addiction. Neuron 59, 11–34 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bonomo, Y.A., Bowes, G., Coffey, C., Carlin, J.B. & Patton, G.C. Teenage drinking and the onset of alcohol dependence: a cohort study over seven years. Addiction 99, 1520–1528 (2004).

    Article  PubMed  Google Scholar 

  3. Jennison, K.M. The short-term effects and unintended long-term consequences of binge drinking in college: a 10-year follow-up study. Am. J. Drug Alcohol Abuse 30, 659–684 (2004).

    Article  PubMed  Google Scholar 

  4. Saha, T.D., Stinson, F.S. & Grant, B.F. The role of alcohol consumption in future classifications of alcohol use disorders. Drug Alcohol Depend. 89, 82–92 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Koob, G.F. Alcoholism: allostasis and beyond. Alcohol. Clin. Exp. Res. 27, 232–243 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Lindell, S.G. et al. Functional NPY variation as a factor in stress resilience and alcohol consumption in rhesus macaques. Arch. Gen. Psychiatry 67, 423–431 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Barr, C.S. et al. CRH haplotype as a factor influencing cerebrospinal fluid levels of corticotropin-releasing hormone, hypothalamic-pituitary-adrenal axis activity, temperament, and alcohol consumption in rhesus macaques. Arch. Gen. Psychiatry 65, 934–944 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ilveskoski, E. et al. Association of neuropeptide y polymorphism with the occurrence of type 1 and type 2 alcoholism. Alcohol. Clin. Exp. Res. 25, 1420–1422 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Chen, A.C. et al. Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence. Alcohol. Clin. Exp. Res. 34, 988–996 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Heilig, M. The NPY system in stress, anxiety and depression. Neuropeptides 38, 213–224 (2004).

    Article  CAS  PubMed  Google Scholar 

  11. Hansson, A.C., Rimondini, R., Neznanova, O., Sommer, W.H. & Heilig, M. Neuroplasticity in brain reward circuitry following a history of ethanol dependence. Eur. J. Neurosci. 27, 1912–1922 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Heilig, M. & Koob, G.F. A key role for corticotropin-releasing factor in alcohol dependence. Trends Neurosci. 30, 399–406 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kash, T.L. & Winder, D.G. Neuropeptide Y and corticotropin-releasing factor bi-directionally modulate inhibitory synaptic transmission in the bed nucleus of the stria terminalis. Neuropharmacology 51, 1013–1022 (2006).

    Article  CAS  PubMed  Google Scholar 

  14. Valdez, G.R. & Koob, G.F. Allostasis and dysregulation of corticotropin-releasing factor and neuropeptide Y systems: implications for the development of alcoholism. Pharmacol. Biochem. Behav. 79, 671–689 (2004).

    Article  CAS  PubMed  Google Scholar 

  15. Valdez, G.R., Sabino, V. & Koob, G.F. Increased anxiety-like behavior and ethanol self-administration in dependent rats: reversal via corticotropin-releasing factor-2 receptor activation. Alcohol. Clin. Exp. Res. 28, 865–872 (2004).

    Article  CAS  PubMed  Google Scholar 

  16. Roberto, M. et al. Corticotropin releasing factor-induced amygdala gamma-aminobutyric acid release plays a key role in alcohol dependence. Biol. Psychiatry 67, 831–839 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sommer, W.H. et al. Upregulation of voluntary alcohol intake, behavioral sensitivity to stress, and amygdala crhr1 expression following a history of dependence. Biol. Psychiatry 63, 139–145 (2008).

    Article  PubMed  Google Scholar 

  18. Lowery-Gionta, E.G. et al. Corticotropin releasing factor signaling in the central amygdala is recruited during binge-like ethanol consumption in C57BL/6J mice. J. Neurosci. 32, 3405–3413 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Heilig, M., Soderpalm, B., Engel, J.A. & Widerlov, E. Centrally administered neuropeptide Y (NPY) produces anxiolytic-like effects in animal anxiety models. Psychopharmacology (Berl.) 98, 524–529 (1989).

    Article  CAS  Google Scholar 

  20. Sparrow, A.M. et al. Central neuropeptide Y modulates binge-like ethanol drinking in C57BL/6J mice via Y1 and Y2 receptors. Neuropsychopharmacology 37, 1409–1421 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhang, H. et al. Neuropeptide Y signaling in the central nucleus of amygdala regulates alcohol-drinking and anxiety-like behaviors of alcohol-preferring rats. Alcohol. Clin. Exp. Res. 34, 451–461 (2010).

    Article  CAS  PubMed  Google Scholar 

  22. Koob, G.F. Brain stress systems in the amygdala and addiction. Brain Res. 1293, 61–75 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Silberman, Y. & Winder, D.G. Emerging role for corticotropin releasing factor signaling in the bed nucleus of the stria terminalis at the intersection of stress and reward. Front. Psychiatry 4, 42 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Eiler, W.J. II, Seyoum, R., Foster, K.L., Mailey, C. & June, H.L. D1 dopamine receptor regulates alcohol-motivated behaviors in the bed nucleus of the stria terminalis in alcohol-preferring (P) rats. Synapse 48, 45–56 (2003).

    Article  CAS  PubMed  Google Scholar 

  25. Hyytiä, P. & Koob, G.F. GABAA receptor antagonism in the extended amygdala decreases ethanol self-administration in rats. Eur. J. Pharmacol. 283, 151–159 (1995).

    Article  PubMed  Google Scholar 

  26. Kash, T.L., Baucum, A.J. II, Conrad, K.L., Colbran, R.J. & Winder, D.G. Alcohol exposure alters NMDAR function in the bed nucleus of the stria terminalis. Neuropsychopharmacology 34, 2420–2429 (2009).

    Article  CAS  PubMed  Google Scholar 

  27. McElligott, Z.A. & Winder, D.G. Modulation of glutamatergic synaptic transmission in the bed nucleus of the stria terminalis. Prog. Neuropsychopharmacol. Biol. Psychiatry 33, 1329–1335 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Thiele, T.E., Crabbe, J.C. & Boehm, S.L. II. “Drinking in the Dark” (DID): a simple mouse model of binge-like alcohol intake. Curr. Protoc. Neurosci. 68 9.49.1–9.49.12 (2014).

  29. Molosh, A.I. et al. NPY Y1 receptors differentially modulate GABAA and NMDA receptors via divergent signal-transduction pathways to reduce excitability of amygdala neurons. Neuropsychopharmacology 38, 1352–1364 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kopp, J. et al. Expression of the neuropeptide Y Y1 receptor in the CNS of rat and of wild-type and Y1 receptor knock-out mice. Focus on immunohistochemical localization. Neuroscience 111, 443–532 (2002).

    Article  CAS  PubMed  Google Scholar 

  31. Rhodes, J.S., Best, K., Belknap, J.K., Finn, D.A. & Crabbe, J.C. Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice. Physiol. Behav. 84, 53–63 (2005).

    Article  CAS  PubMed  Google Scholar 

  32. Calzá, L. et al. Daily changes of neuropeptide Y-like immunoreactivity in the suprachiasmatic nucleus of the rat. Regul. Pept. 27, 127–137 (1990).

    Article  PubMed  Google Scholar 

  33. Parker, S.L. et al. Cloned neuropeptide Y (NPY) Y1 and pancreatic polypeptide Y4 receptors expressed in Chinese hamster ovary cells show considerable agonist-driven internalization, in contrast to the NPY Y2 receptor. Eur. J. Biochem. 268, 877–886 (2001).

    Article  CAS  PubMed  Google Scholar 

  34. Grant, K.A. et al. Drinking typography established by scheduled induction predicts chronic heavy drinking in a monkey model of ethanol self-administration. Alcohol. Clin. Exp. Res. 32, 1824–1838 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sparta, D.R. et al. Blockade of the corticotropin releasing factor type 1 receptor attenuates elevated ethanol drinking associated with drinking in the dark procedures. Alcohol. Clin. Exp. Res. 32, 259–265 (2008).

    Article  CAS  PubMed  Google Scholar 

  36. Pleil, K.E. et al. Chronic stress alters neuropeptide Y signaling in the bed nucleus of the stria terminalis in DBA/2J but not C57BL/6J mice. Neuropharmacology 62, 1777–1786 (2012).

    Article  CAS  PubMed  Google Scholar 

  37. Li, H. et al. Experience-dependent modification of a central amygdala fear circuit. Nat. Neurosci. 16, 332–339 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cippitelli, A. et al. Pharmacological blockade of corticotropin-releasing hormone receptor 1 (CRH1R) reduces voluntary consumption of high alcohol concentrations in non-dependent Wistar rats. Pharmacol. Biochem. Behav. 100, 522–529 (2012).

    Article  CAS  PubMed  Google Scholar 

  39. Ron, D. & Messing, R.O. Signaling pathways mediating alcohol effects. Curr. Top. Behav. Neurosci. 13, 87–126 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sparta, D.R. et al. Binge ethanol-drinking potentiates corticotropin releasing factor R1 receptor activity in the ventral tegmental area. Alcohol. Clin. Exp. Res. 37, 1680–1687 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Melis, M., Camarini, R., Ungless, M.A. & Bonci, A. Long-lasting potentiation of GABAergic synapses in dopamine neurons after a single in vivo ethanol exposure. J. Neurosci. 22, 2074–2082 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Moore, E.M. et al. GABAergic modulation of binge-like ethanol intake in C57BL/6J mice. Pharmacol. Biochem. Behav. 88, 105–113 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Borghese, C.M. & Harris, R.A. Alcohol dependence and genes encoding alpha2 and gamma1 GABAA Receptor subunits: insights from humans and mice. Alcohol. Res. 34, 345–353 (2012).

    PubMed  PubMed Central  Google Scholar 

  44. Cox, B.R. et al. Repeated cycles of binge-like ethanol (EtOH)-drinking in male C57BL/6J mice augments subsequent voluntary ethanol intake but not other dependence-like phenotypes. Alcohol. Clin. Exp. Res. 37, 1688–1695 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Pandey, S.C., Carr, L.G., Heilig, M., Ilveskoski, E. & Thiele, T.E. Neuropeptide y and alcoholism: genetic, molecular, and pharmacological evidence. Alcohol. Clin. Exp. Res. 27, 149–154 (2003).

    Article  PubMed  Google Scholar 

  46. Gilpin, N.W. et al. Neuropeptide Y opposes alcohol effects on gamma-aminobutyric acid release in amygdala and blocks the transition to alcohol dependence. Biol. Psychiatry 69, 1091–1099 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Krashes, M.J. et al. An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger. Nature 507, 238–242 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Helms, C.M. et al. The effects of age at the onset of drinking to intoxication and chronic ethanol self-administration in male rhesus macaques. Psychopharmacology (Berl.) 231, 1853–1861 (2014).

    Article  CAS  Google Scholar 

  49. Pinto, S. et al. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 304, 110–115 (2004).

    Article  CAS  PubMed  Google Scholar 

  50. Brumovsky, P. et al. Neuropeptide Y2 receptor protein is present in peptidergic and nonpeptidergic primary sensory neurons of the mouse. J. Comp. Neurol. 489, 328–348 (2005).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank S. Chien for assistance with histological verification of DREADD virus and cannulae placements, R. Thomas and G. Sprow for help with drinking behavior experiments, and B. Roth (UNC School of Medicine) for viral constructs and CNO. This work was supported by US National Institutes of Health grants AA021043 to K.E.P.; AA019454, AA020911 and AA011605 to T.L.K.; AA013573 and AA022048 to T.E.T.; AA013541 and AA109431 to K.A.G.; DK071561 to D.P.O.; and DK075632, DK096010, DK046200 and DK057521 to B.B.L., and by the Bowles Center for Alcohol Studies at the University of North Carolina School of Medicine.

Author information

Authors and Affiliations

Authors

Contributions

K.E.P. wrote the manuscript, designed the study, performed all electrophysiological recordings, and performed in vivo behavioral pharmacology, in vivo DREADD DID experiments and immunohistochemistry. J.A.R. performed cannulation and DREADD viral injection surgeries and in vivo behavioral pharmacology and DREADD DID experiments. E.G.L.-G. performed cannulation surgeries and in vivo behavioral pharmacology experiments. C.M.M. performed cannulation surgeries, fluorescence and confocal microscope imaging of DREADD expression, and pilot experiments for DREADD constructs and CNO doses. N.M.M. performed RT-PCR and immunohistochemistry and bred CRF-Cre and CRF reporter mice. A.M.K. performed cannulation surgeries and bred CRF-Cre and CRF reporter mice. D.P.O. and B.B.L. generated the CRF-ires-Cre (Crh-ires-Cre) mice. K.A.G. oversaw rhesus monkey experiments and provided monkey brain tissue. T.E.T. aided in the design of and oversaw all behavioral experiments. T.L.K. helped to design the study and write the manuscript, and oversaw all molecular biology, microscopy and electrophysiology work. All of the authors edited the manuscript.

Corresponding author

Correspondence to Thomas L Kash.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Manipulation of Y1R and Y2R in the BNST alters binge-like ethanol drinking during 3-cycle DID and sucrose consumption.

(a) Standard Drinking-in-the-Dark (DID) voluntary ethanol consumption paradigm (1 cycle depicted), where mice are given 2 h of access to 20% ethanol three hours into the dark cycle on three consecutive days, followed by 4 h of access on the fourth, binge test day. (b) Bilateral infusion of the Y1R agonist LeuPro NPY (99 pmol/200 nL/side) into the BNST-adjacent dorsal striatum prior to ethanol access on cycle 3 Day 4 of DID did not alter binge ethanol consumption (unpaired t-test with Welch’s correction: p > 0.65; CON N = 6, LeuPro N = 7), suggesting the decrease in binge drinking shown in Figure 1b was specific to the BNST. (c−g) Bilateral intra-BNST infusion of the Y1R antagonist BIBP 3226 trifluoroacetate (BIBP 3226; 20 pmol/200 nL/side) prior to ethanol access on cycle 3 Day 4 of DID did not alter ethanol consumption during the first 2-h epoch of the binge session (c; unpaired t-test: p > 0.20; CON N = 7, BIBP N = 7) but did increase ethanol consumption during the second 2-hr epoch (d; t(12) = 3.94, **p = 0.002); it had no effect on the percent time in center (e) or locomotor behavior (f) in the OF (p’s > 0.45; CON N = 7, BIBP N = 5) or on sucrose drinking on Day 4 of sucrose DID (g; p > 0.75; CON N = 7, BIBP N = 6). (h−l) Bilateral intra-BNST infusion of the Y2R agonist neuropeptide Y 13−36 (NPY 13−36; 100 pmol/200 nL/side) did not alter ethanol consumption during the first 2−h epoch of the binge session (h; unpaired t-test: p > 0.20; CON N = 7, NPY 13-36 N = 8) but did increase ethanol consumption during the second 2−h epoch (i; t(13) = 2.24, *p = 0.044); it had no effect on the percent time in center (j) or locomotor behavior (k) in the OF (p’s > 0.65; CON N = 9, NPY 13-36 N = 7); NPY 13-36 decreased binge sucrose consumption on Day 4 of sucrose DID (l; t(14) = 2.25, *p = 0.041; CON N = 7, NPY 13-36 N = 9). (m−q) Bilateral intra-BNST infusion of the Y2R antagonist BIIE 0246 (120 pmol/200 nL/side) did not alter any measures in ethanol DID (CON N = 9, BIIE N = 8), OF (CON N = 8, BIIE N = 9), or sucrose DID (CON N = 7, BIIE N = 10; unpaired t-tests: p’s > 0.25). All data in b−q are presented as mean ± SEM.

Supplementary Figure 2 Manipulation of Y1R, but not Y2R, in the BNST alters binge-like ethanol drinking during 2-cycle DID.

(a−b) Mice that received bilateral intra-BNST infusions of LeuPro NPY prior to access to EtOH on Cycle 2 Day 4 consumed significantly less ethanol than CON mice (a; unpaired t-test: t(12) = 2.49, *p = 0.029; CON N = 8, LeuPro N = 6), but locomotor behavior in the OF was unaffected (b; p > 0.90; CON N = 6, LeuPro N = 9). (c−d) Bilateral intra-BNST infusions of BIIE 0246 did not alter binge ethanol consumption in 2-cycle DID (c; CON N = 3, BIIE N = 5) or locomotor behavior in the OF (d; CON N = 3, BIIE N = 4; unpaired t-tests: p’s > 0.70). All data are presented as mean ± SEM.

Supplementary Figure 3 Y1R activation alters GABAergic transmission via a PKA-dependent mechanism without altering cell membrane or dendritic excitability.

(a) Bath pre-application of the PKA inhibitor Rp-cAMPs (10 µM; n = 5, N = 3), but not the PLC inhibitor U73122 (10 µM; n = 5, N = 3), blocked the ability of subsequently applied LeuPro NPY (300 nM) to increase mIPSC frequency (paired t-tests baseline vs. washout: p > 0.35 and t(4) = 4.72, **p = 0.009, respectively); LeuPro NPY did not alter mIPSC amplitude under either condition (p’s > 0.75). (b) Mean basal mIPSC frequency in BNST neurons is increased by pipette inclusion of NEM (t(31) = 3.63, **p < 0.003) and BAPTA (t(37) = 3.28, *p = 0.010), but no other drugs included in the recording pipette (p’s > 0.25; n’s are identical to Fig. 1k), when corrected for multiple comparisons with Sidak’s multiple comparisons tests. (c-d) Postsynaptic membrane resistance was not altered by bath application of LeuPro NPY (c; paired t-test baseline vs. washout: p > 0.60; n = 13, N = 11 as in Fig. 1i), and bath application of LeuPro NPY increased mIPSC frequency (t(5) = 3.15, p = 0.025; n = 6, N = 3) but not amplitude (p > 0.85) when a Cs-based intracellular solution was used, similar to the effect achieved using a K+-based solution (d), as in Fig. 1i, suggesting that effects of LeuPro NPY do not require K+ channels. All data are presented as mean ± SEM.

Supplementary Figure 4 mRNA for NPY and its receptors are unaltered following 3-cycle DID.

(a) Mice that underwent 3-cycle EtOH DID consistently consumed an average of 6.4−7.2 g/kg ethanol and achieved blood ethanol contents (BECs) of approximately 162 mg/dl (N = 9). (b−d) mRNA content of NPY (b; N’s = 10), Y1R (c; N’s = 10), and Y2R (d; CON n = 8, EtOH n = 9) in the BNST was not different between ethanol drinkers and controls one day following 3-cycle DID (unpaired t-tests: p’s > 0.65). All data are presented as mean ± SEM.

Supplementary Figure 5 Y1R-mediated inhibition of BNST CRF neurons occurs via postsynaptic Gi signaling.

(a) Model depiction of the mechanism of Y1R−mediated modulation of binge alcohol drinking, in which activation of postsynaptic Gi-coupled Y1R on CRF neurons in the BNST inhibits PKA to increase the surface expression of GABAAR, leading to postsynaptic inhibition of the CRF neurons. (b) Representative trace from a whole-cell current-clamp electrophysiological recording showing that bath application of CNO (10 µM) hyperpolarizes Gi-DREADD-expressing CRF-Cre neurons in the BNST. (c) Average magnitude of hyperpolarization of Gi-DREADD-expressing CRF−Cre neurons in the BNST after bath application of CNO (paired t-test baseline vs. CNO: t(8) = 4.03, **p = 0.004; n = 9, N = 4; data are presented as mean ± SEM).

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pleil, K., Rinker, J., Lowery-Gionta, E. et al. NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking. Nat Neurosci 18, 545–552 (2015). https://doi.org/10.1038/nn.3972

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.3972

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing