A study recently published in Biological Psychiatry has uncovered new information on the brain circuitry involved in binge drinking, elucidating a mechanism that may lead to future pharmacologic treatments.1 Binge drinking is defined by the National Institute on Alcohol Abuse and Alcoholism as “a pattern of drinking alcohol that brings blood alcohol concentration (BAC) to 0.08 gram percent or above,” an effect that typically occurs following the consumption of 5 or more drinks within 2 hours by men, or the consumption of 4 or more drinks within 2 hours by women.2 Binge drinking, a public health issue responsible for more than $170 billion in excess costs,3 has been implicated in the development of alcohol dependence.
The role played by corticotropin-releasing factor (CRF) receptors in alcohol and drug abuse has been a topic of active investigation for the last 2 decades.4 Studies involving rodents have demonstrated that ethanol consumption is modulated by CRF signaling in the ventral tegmental area (VTA), a brain structure involved in reward and motivation. Rodent studies have likewise demonstrated a role for CRF signaling in the modulation of binge-like ethanol consumption. This study, by investigators from the Behavioral Neuroscience Program in the Department of Psychology & Neuroscience University of North Carolina at Chapel Hill, employed a number of measures to assess how the VTA CRF system in mice would be impacted by binge-like ethanol consumption using a drinking-in-the-dark protocol. Infusions of selective CRF compounds into cannulas aimed at the VTA were employed to determine the role of these receptors in modulating binge-like ethanol consumption. To assess the contribution of CRF projections from the bed nucleus of the stria terminalis (BNST) to the VTA, investigators chemogenetically inhibited the CRF neurons in this circuit in vivo. The investigators also measured binge-induced changes in VTA CRF system protein and messenger RNA.
“In this study, we show that intra-VTA CRF1R antagonism and CRF2R activation both significantly decreased binge-like ethanol consumption and that reductions in binge-like drinking secondary to CRF1R blockade were dependent on intact CRF2R signaling. Additionally, we show that CRF projections from the BNST to the VTA, but not local VTA CRF neurons, are involved in modulating binge-like ethanol drinking. Finally, binge-like ethanol consumption was sufficient to induce increased CRF mRNA expression within the VTA, associated with a significant decrease in CRF1R protein levels,” explained the authors.
“The CRF signaling in the VTA that modulates binge-like ethanol drinking arises from a circuit originating in the BNST and likely involves heteroregulation of GABA signaling from the same neurons. These observations reinforce the idea that targets aimed at the central CRF system may be therapeutic in treating alcohol use disorders,” the authors concluded.
“The puzzle is starting to come together, and is telling us more than we ever knew about before,” commented co-investigator Todd Thiele, PhD, of the Behavioral Neuroscience Program in the Department of Psychology & Neuroscience University of North Carolina at Chapel Hill in a press release. “We now know that 2 brain regions that modulate stress and reward are part of a functional circuit that controls binge drinking and adds to the idea that manipulating the CRF system is an avenue for treating it.”3
- Rinker JA, Marshall SA, Mazzone CM, et al. Extended amygdala to ventral tegmental area corticotropin-releasing factor circuit controls binge ethanol intake. Biol Psychiatry. 2016; Mar [Epub ahead of print]
- Drinking Levels Defined. National Institute on Alcohol Abuse and Alcoholism (NIAAA). http://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking. Accessed May 9, 2016.
- Researchers find brain circuit that controls binge drinking [news release]. Chapel Hill, NC: UNC Communications and Public Affairs; April 26, 2016. http://http://uncnews.unc.edu/2016/04/26/researchers-find-brain-circuit-controls-binge-drinking. Accessed May 8, 2016.
- Palmer AA, Sharpe AL, Burkhart-Kasch S, et al. Corticotropin-releasing factor overexpression decreases ethanol drinking and increases sensitivity to the sedative effects of ethanol. Psychopharmacology (Berl). 2004;176(3-4):386-397.