Abstract
Background
Corticotropin-releasing factor (CRF) signaling at the CRF1 receptor (CRF1R) in the ventral tegmental area (VTA) can modulate ethanol consumption in rodents.
However, the effects of binge-like ethanol drinking on this system have not been thoroughly
characterized, and little is known about the role of CRF2R or the CRF neurocircuitry involved.
Methods
The effects of binge-like ethanol consumption on the VTA CRF system were assessed
following drinking-in-the-dark procedures. Intra-VTA infusions of selective CRF1R and/or CRF2R compounds were employed to assess the contributions of these receptors in modulating
binge-like ethanol consumption (n = 89). To determine the potential role of CRF projections from the bed nucleus of
the stria terminalis (BNST) to the VTA, CRF neurons in this circuit were chemogenetically
inhibited (n = 32). Binge-induced changes in VTA CRF system protein and messenger RNA were also
assessed (n = 58).
Results
Intra-VTA antagonism of CRF1R and activation of CRF2R resulted in decreased ethanol intake, which was eliminated by simultaneous blockade
of both receptors. Chemogenetic inhibition of local CRF neurons in the VTA did not
alter binge-like ethanol drinking, but inhibition of VTA-projecting CRF neurons from
the BNST significantly reduced intake.
Conclusions
We provide novel evidence that 1) blunted binge-like ethanol consumption stemming
from CRF1R blockade requires intact CRF2R signaling, and CRF2R activation reduces binge-like drinking; 2) inhibiting VTA-projecting BNST CRF neurons
attenuates binge-like drinking; and 3) binge-like ethanol drinking alters protein
and messenger RNA associated with the VTA-CRF system. These data suggest that ethanol-induced
activation of BNST-to-VTA CRF projections is critical in driving binge-like ethanol
intake.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- National Institute on Alcohol Abuse and Alcoholism Council approves definition of binge drinking.NIAAA Newsletter. U.S. Department of Health and Human Services, National Institutes of Health. p, 2004: 3
- 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. 2004; 30: 659-684
- Continuity of binge and harmful drinking from late adolescence to early adulthood.Pediatrics. 2004; 114: 714-719
- Corticotropin releasing factor-induced amygdala gamma-aminobutyric acid release plays a key role in alcohol dependence.Biol Psychiatry. 2010; 67: 831-839
- Corticotropin releasing factor (CRF) receptor signaling in the central nervous system: New molecular targets.CNS Neurol Disord Drug Targets. 2006; 5: 453-479
- Localization of novel corticotropin-releasing factor receptor (CRF2) mRNA expression to specific subcortical nuclei in rat brain: Comparison with CRF1 receptor mRNA expression.J Neurosci. 1995; 15: 6340-6350
- Effects of CRF1-receptor and opioid-receptor antagonists on dependence-induced increases in alcohol drinking by alcohol-preferring (P) rats.Alcohol Clin Exp Res. 2008; 32: 1535-1542
- Increased ethanol self-administration and anxiety-like behavior during acute ethanol withdrawal and protracted abstinence: Regulation by corticotropin-releasing factor.Alcohol Clin Exp Res. 2002; 26: 1494-1501
- Increased anxiety-like behavior and ethanol self-administration in dependent rats: Reversal via corticotropin-releasing factor-2 receptor activation.Alcohol Clin Exp Res. 2004; 28: 865-872
- Increased drinking during withdrawal from intermittent ethanol exposure is blocked by the CRF receptor antagonist D-Phe-CRF(12-41).Alcohol Clin Exp Res. 2007; 31: 939-949
- Pre-clinical evidence that corticotropin-releasing factor (CRF) receptor antagonists are promising targets for pharmacological treatment of alcoholism.CNS Neurol Disord Drug Targets. 2010; 9: 77-86
- CRF-1 antagonist and CRF-2 agonist decrease binge-like ethanol drinking in C57BL/6J mice independent of the HPA axis.Neuropsychopharmacology. 2010; 35: 1241-1252
- Corticotropin releasing factor signaling in the central amygdala is recruited during binge-like ethanol consumption in C57BL/6J mice.J Neurosci. 2012; 32: 3405-3413
- Alcohol in excess: CRF(1) receptors in the rat and mouse VTA and DRN.Psychopharmacology (Berl). 2013; 225: 313-327
- Binge ethanol-drinking potentiates corticotropin releasing factor R1 receptor activity in the ventral tegmental area.Alcohol Clin Exp Res. 2013; 37: 1680-1687
- NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking.Nat Neurosci. 2015; 18: 545-552
- Chronic cocaine enhances corticotropin-releasing factor-dependent potentiation of excitatory transmission in ventral tegmental area dopamine neurons.J Neurosci. 2009; 29: 6535-6544
- A ventral tegmental CRF-glutamate-dopamine interaction in addiction.Brain Res. 2010; 1314: 38-43
- Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.Proc Natl Acad Sci U S A. 1988; 85: 5274-5278
- The role of mesolimbic dopamine in the development and maintenance of ethanol reinforcement.Pharmacol Ther. 2004; 103: 121-146
- An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger.Nature. 2014; 507: 238-242
- Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice.Physiol Behav. 2005; 84: 53-63
- “Drinking in the Dark” (DID): A simple mouse model of binge-like alcohol intake.Curr Protoc Neurosci. 2014; 68: 9.49.1-9.49.12
- Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand.Proc Natl Acad Sci U S A. 2007; 104: 5163-5168
- Theta oscillations regulate the speed of locomotion via a hippocampus to lateral septum pathway.Nat Commun. 2015; 6: 8521
- Designer receptors show role for ventral pallidum input to ventral tegmental area in cocaine seeking.Nat Neurosci. 2014; 17: 577-585
- Chemogenetic synaptic silencing of neural circuits localizes a hypothalamus-->midbrain pathway for feeding behavior.Neuron. 2014; 82: 797-808
- Corticotropin releasing factor binding protein and CRF2 receptors in the ventral tegmental area: Modulation of ethanol binge drinking in C57BL/6J mice.Alcohol Clin Exp Res. 2015; 39: 1609-1618
- Novel roles for CRF-binding protein and CRF receptor 2 in binge drinking.Alcohol Clin Exp Res. 2015; 39: 2296-2298
- Corticotropin-releasing factor projections from limbic forebrain and paraventricular nucleus of the hypothalamus to the region of the ventral tegmental area.Neuroscience. 2007; 150: 8-13
- Central CRF neurons are not created equal: Phenotypic differences in CRF-containing neurons of the rat paraventricular hypothalamus and the bed nucleus of the stria terminalis.Front Neurosci. 2013; 7: 156
- GABAA receptors in the posterior, but not anterior, ventral tegmental area mediate Ro15-4513-induced attenuation of binge-like ethanol consumption in C57BL/6J female mice.Behav Brain Res. 2011; 220: 230-237
- VTA CRF neurons mediate the aversive effects of nicotine withdrawal and promote intake escalation.Nat Neurosci. 2014; 17: 1751-1758
- Agonist-induced internalization of corticotropin-releasing factor receptors in noradrenergic neurons of the rat locus coeruleus.Eur J Neurosci. 2006; 23: 2991-2998
- Stress-induced intracellular trafficking of corticotropin-releasing factor receptors in rat locus coeruleus neurons.Endocrinology. 2008; 149: 122-130
- Stress-induced redistribution of corticotropin-releasing factor receptor subtypes in the dorsal raphe nucleus.Biol Psychiatry. 2009; 66: 76-83
- Using high resolution imaging to determine trafficking of corticotropin-releasing factor receptors in noradrenergic neurons of the rat locus coeruleus.Life Sci. 2014; 112: 2-9
- Presynaptic CRF1 receptors mediate the ethanol enhancement of GABAergic transmission in the mouse central amygdala. Sci.World J. 2009; 9: 68-85
- CRF-R2 and the heterosynaptic regulation of VTA glutamate during reinstatement of cocaine seeking.J Neurosci. 2014; 34: 10402-10414
Article Info
Publication History
Published online: March 03, 2016
Accepted:
February 22,
2016
Received in revised form:
February 6,
2016
Received:
July 22,
2015
Identification
Copyright
© Society of Biological Psychiatry, 2016.
