| First Author | Burnham NW | Year | 2021 |
| Journal | Neuropharmacology | Volume | 196 |
| Pages | 108702 | PubMed ID | 34246685 |
| Mgi Jnum | J:319425 | Mgi Id | MGI:6789797 |
| Doi | 10.1016/j.neuropharm.2021.108702 | Citation | Burnham NW, et al. (2021) Lateral hypothalamus-projecting noradrenergic locus coeruleus pathway modulates binge-like ethanol drinking in male and female TH-ires-cre mice. Neuropharmacology 196:108702 |
| abstractText | A growing body of literature implicates noradrenergic (NE) signaling in the modulation of ethanol consumption. However, relatively few studies have detailed specific brain pathways that mediate NE-associated binge-like ethanol consumption. To begin to fill this gap in the literature, male and female C57BL6/J and TH-ires-cre mice underwent pharmacological and chemogenetic testing, respectively, in combination with "drinking in the dark" procedures to model binge-like consumption of ethanol or sucrose solutions. First, we showed that intraperitoneal administration of the NE reuptake inhibitor, reboxetine, blunted binge-like ethanol intake in C57BL6/J mice. Chemogenetic activation of locus coeruleus (LC) tyrosine hydroxylase (TH)-expressing neurons blunted binge-like ethanol intake regardless of sex. Chemogenetic activation of LC projections to the lateral hypothalamus (LH), a region implicated in ethanol consumption, blunted binge-like ethanol drinking without altering sucrose intake in ethanol-experienced or ethanol-naive mice. In C57BL/6 J mice, LH-targeted microinfusion of an alpha1-adrenergic receptor (AR) agonist blunted binge-like ethanol intake across both sexes, while LH infusion of a beta-AR agonist blunted binge-like ethanol intake in females exclusively. Finally, in mice with high baseline ethanol intake both an alpha1- AR agonist and an alpha-2 AR antagonist blunted binge-like ethanol intake. The present results provide novel evidence that increased NE tone in a circuit arising from the LC and projecting to the LH reduces binge-like ethanol drinking in mice, and may represent a novel approach to treating binge or heavy drinking prior to the development of dependence. This article is part of the special Issue on "Neurocircuitry Modulating Drug and Alcohol Abuse". |
