Social stress-escalated intermittent alcohol drinking: modulation by CRF-R1 in the ventral tegmental area and accumbal dopamine in mice

Hwa, Lara S.; Holly, Elizabeth N.; DeBold, Joseph F.; Miczek, Klaus A.

doi:10.1007/s00213-015-4144-2

Cited by 54 publications

(57 citation statements)

References 53 publications

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“…Moreover, prolonged exposure to corticosterone in vitro (in midbrain slices) was sufficient to induce neuroadaptations associated with in vivo stress. These findings highlight the importance of glucocorticoid signaling within the VTA, but we do not rule out the participation of other stress signaling molecules or hormones, such as CRF, in mediating stress-induced adaptations (Hwa et al, 2016; Ungless et al, 2003). Furthermore, the effect of glucocorticoids on VTA GABA neurons may involve the activity of noradrenaline, glutamate, and glial cells (Coull et al, 2003; Hewitt et al, 2009; Lee et al, 2011; Taylor et al, 2015).…”

Section: Discussionmentioning

confidence: 61%

Stress Increases Ethanol Self-Administration via a Shift toward Excitatory GABA Signaling in the Ventral Tegmental Area

Ostroumov

Thomas

Kimmey

et al. 2016

Neuron

149

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SUMMARY Stress is a well-known risk factor for subsequent alcohol abuse, but the neural mechanisms underlying interactions between stress and alcohol remain largely unknown. Addictive drug reinforcement and stress signaling involve common neural circuitry, including the mesolimbic dopamine system. We demonstrate in rodents that pre-exposure to stress attenuates alcohol-induced dopamine responses and increases alcohol self-administration. The blunted dopamine signaling resulted from ethanol-induced excitation of GABA neurons in the ventral tegmental area. Excitation of GABA neurons was mediated by GABAA receptor activation and involved stress-induced functional down-regulation of the K+, Cl− cotransporter, KCC2. Blocking stress hormone receptors, enhancing KCC2 function, or preventing excitatory GABA signaling by alternative methods all prevented the attenuated alcohol-induced dopamine response and prevented the increased alcohol self-administration. These results demonstrate that stress alters the neural and behavioral responses to alcohol through a neuroendocrine signal that shifts inhibitory GABA transmission towards excitation.

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Section: Discussionmentioning

confidence: 61%

Stress Increases Ethanol Self-Administration via a Shift toward Excitatory GABA Signaling in the Ventral Tegmental Area

Ostroumov

Thomas

Kimmey

et al. 2016

Neuron

149

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“…1 and Table 1), mice first had one 24-h session of alcohol-only drinking under two-bottle choice (one bottle with 15% alcohol in water, one bottle with water), and then a 24-h withdrawal period. A 24-h period was chosen since it is utilized in other widely used models of intermittent-access alcohol drinking (e.g., Hwa et al, 2016 and Warnault et al, 2016). Thereafter, mice drank under a Limited Daily Access (LDA) paradigm, with 2 h/day, 5 days/week of two-bottle choice starting ~3 h into the dark cycle each day.…”

Section: Methodsmentioning

confidence: 99%

A single alcohol drinking session is sufficient to enable subsequent aversion-resistant consumption in mice

Lei

Wegner

et al. 2016

Alcohol

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Addiction is mediated in large part by pathological motivation for rewarding, addictive substances, and alcohol-use disorders (AUDs) continue to extract a very high physical and economic toll on society. Compulsive alcohol drinking, where intake continues despite negative consequences, is considered a particular obstacle during treatment of AUDs. Aversion-resistant drives for alcohol have been modeled in rodents, where animals continue to consume even when alcohol is adulterated with the bitter tastant quinine, or is paired with another aversive consequence. Here, we describe a two-bottle choice paradigm where C57BL/6 mice first had 24-h access to 15% alcohol or water. Afterward, they drank quinine-free alcohol (alcohol-only) or alcohol with quinine (100 μM), in a limited daily access (LDA) two-bottle-choice paradigm (2 h/day, 5 days/week, starting 3 h into the dark cycle), and achieved nearly binge-level blood alcohol concentrations. Interestingly, a single, initial 24-h experience with alcohol-only enhanced subsequent quinine-resistant drinking. In contrast, mice that drank alcohol–quinine in the 24-h session showed significantly reduced alcohol–quinine intake and preference during the subsequent LDA sessions, relative to mice that drank alcohol-only in the initial 24-h session and alcohol–quinine in LDA sessions. Thus, mice could find the concentration of quinine we used aversive, but were able to disregard the quinine after a single alcohol-only drinking session. Finally, mice had low intake and preference for quinine in water, both before and after weeks of alcohol-drinking sessions, suggesting that quinine resistance was not a consequence of increased quinine preference after weeks of drinking of alcohol–quinine. Together, we demonstrate that a single alcohol-only session was sufficient to enable subsequent aversion-resistant consumption in C57BL/6 mice, which did not reflect changes in quinine taste palatability. Given the rapid development of quinine-resistant alcohol drinking patterns, this model provides a simple, quick, and robust method for uncovering the mechanisms that promote aversion-resistant consumption.

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“…In fact, direct infusion of a CRF antagonist into the median raphe nucleus blocked stress-induced alcohol seeking behavior (Funk et al, 2003; Le et al, 2002; Le et al, 2013). CRF 1 receptor antagonists injected into the ventral tegmental area reduced alcohol intake in high-drinking models, including stress-enhanced drinking (Hwa et al, 2016; Rinker et al, 2016). Overall, while a role for CRF 2 receptors cannot be ruled out (Funk and Koob, 2007; Valdez et al, 2004), the large preponderance of evidence suggests that CRF 1 receptors play an important role in regulating alcohol consumption, especially excessive levels of drinking associated with dependence.…”

Section: Mechanisms Underlying Chronic Alcohol Stress and Drinkimentioning

confidence: 99%

Influence of stress associated with chronic alcohol exposure on drinking

Becker

2017

Neuropharmacology

138

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Stress is commonly regarded as an important trigger for relapse and a significant factor that promotes increased motivation to drink in some individuals. However, the relationship between stress and alcohol is complex, likely changing in form during the transition from early moderated alcohol use to more heavy uncontrolled alcohol intake. A growing body of evidence indicates that prolonged excessive alcohol consumption serves as a potent stressor, producing persistent dysregulation of brain reward and stress systems beyond normal homeostatic limits. This progressive dysfunctional (allostatic) state is characterized by changes in neuroendocrine and brain stress pathways that underlie expression of withdrawal symptoms that reflect a negative affective state (dysphoria, anxiety), as well as increased motivation to self-administer alcohol. This review highlights literature supportive of this theoretical framework for alcohol addiction. In particular, evidence for stress-related neural, physiological, and behavioral changes associated with chronic alcohol exposure and withdrawal experience is presented. Additionally, this review focuses on the effects of chronic alcohol-induced changes in several pro-stress neuropeptides (corticotropin-releasing factor, dynorphin) and anti-stress neuropeptide systems (nocicepton, neuropeptide Y, oxytocin) in contributing to the stress, negative emotional, and motivational consequences of chronic alcohol exposure. Studies involving use of animal models have significantly increased our understanding of the dynamic stress-related physiological mechanisms and psychological underpinnings of alcohol addiction. This, in turn, is crucial for developing new and more effective therapeutics for treating excessive, harmful drinking, particularly stress-enhanced alcohol consumption.

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Social stress-escalated intermittent alcohol drinking: modulation by CRF-R1 in the ventral tegmental area and accumbal dopamine in mice

Cited by 54 publications

References 53 publications

Stress Increases Ethanol Self-Administration via a Shift toward Excitatory GABA Signaling in the Ventral Tegmental Area

Stress Increases Ethanol Self-Administration via a Shift toward Excitatory GABA Signaling in the Ventral Tegmental Area

A single alcohol drinking session is sufficient to enable subsequent aversion-resistant consumption in mice

Influence of stress associated with chronic alcohol exposure on drinking

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