Ethanol intake is increased by injection of galanin in the paraventricular nucleus and reduced by a galanin antagonist

Rada, Pedro; Avena, Nicole M.; Leibowitz, Sarah F.; Hoebel, Bartley G.

doi:10.1016/j.alcohol.2004.05.002

Cited by 46 publications

(33 citation statements)

References 39 publications

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“…Other studies have revealed a stimulatory effect of ethanol drinking on the expression of two non-opioid, orexigenic peptides, galanin and orexin, in the hypothalamus (Lawrence et al, 2006; Leibowitz et al, 2003). Similar to δ-agonists, these peptides are known to stimulate food intake in ethanol-naïve rats, and this effect switches to an increase specifically in ethanol intake in rats trained to drink ethanol (Rada et al, 2004; Schneider et al, 2007). It is interesting that all three orexigenic peptides, enkephalin, galanin, and orexin, are also stimulated by chronic or acute consumption of a fat-rich diet, in a manner similar to ethanol (Chang et al, 2007b; Chang et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Opioids in the Hypothalamic Paraventricular Nucleus Stimulate Ethanol Intake

Barson

Carr

Soun

et al. 2010

Alcoholism Clin & Exp Res

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Background Specialized hypothalamic systems that increase food intake might also increase ethanol intake. To test this possibility, morphine and receptor-specific opioid agonists were microinjected in the paraventricular nucleus (PVN) of rats that had learned to drink ethanol. To cross-validate the results, naloxone methiodide (m-naloxone), an opioid antagonist, was microinjected with the expectation that it would have the opposite effect of morphine and the specific opioid agonists. Methods Sprague-Dawley rats were trained, without sugar, to drink 4% or 7% ethanol and were then implanted with chronic brain cannulas aimed at the PVN. After recovery, those drinking 7% ethanol, with food and water available, were injected with two doses each of morphine or m-naloxone. To test for receptor specificity, two doses each of the μ-receptor agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin (DAMGO), δ-receptor agonist D-Ala-Gly-Phe-Met-NH2 (DALA), or k-receptor agonist U-50,488H were injected. DAMGO was also tested in rats drinking 4% ethanol without food or water available. As an anatomical control for drug reflux, injections were made 2 mm dorsal to the PVN. Results A main result was a significant increase in ethanol intake induced by PVN injection of morphine. The opposite effect was produced by m-naloxone. The effects of morphine and m-naloxone were exclusively on intake of ethanol, even though food and water were freely available. In the analysis with specific receptor agonists, PVN injection of the δ-agonist DALA significantly increased 7% ethanol intake without affecting food or water intake. This is in contrast to the k-agonist U-50,488H, which decreased ethanol intake, and the μ-agonist DAMGO, which had no effect on ethanol intake in the presence or absence of food and water. In the anatomical control location 2 mm dorsal to the PVN, no drug caused any significant changes in ethanol, food, or water intake, providing evidence that the active site was close to the cannula tip. Conclusions The δ-opioid receptor agonist in the PVN increased ethanol intake in strong preference over food and water, while the k-opioid agonist suppressed ethanol intake. Prior studies show that learning to drink ethanol stimulates PVN expression and production of the peptides enkephalin and dynorphin, which are endogenous agonists for the δ- and k-receptors, respectively. These results suggest that enkephalin via the δ-opioid system can function locally within a positive feedback circuit to cause ethanol intake to escalate and ultimately contribute to the abuse of ethanol. This is in contrast to dynorphin via the k-opioid system, which may act to counter this escalation. Naltrexone therapy for alcoholism may act, in part, by blocking the enkephalin-triggered positive feedback cycle.

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Section: Discussionmentioning

confidence: 99%

Opioids in the Hypothalamic Paraventricular Nucleus Stimulate Ethanol Intake

Barson

Carr

Soun

et al. 2010

Alcoholism Clin & Exp Res

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“…Injection of GAL into the PVN of rats has been shown in a variety of paradigms to increase moderate alcohol drinking (bringing blood alcohol levels to 30-60 mg/dl) while a general GAL receptor antagonist decreases it (Chen et al, 2014a; Rada et al, 2004; Schneider et al, 2007). Notably, this stimulatory effect of GAL does not occur with injection in the LH (Schneider et al, 2007), paralleling the finding that hypothalamic GAL increases food intake only when injected into the PVN or adjacent periventricular region (Kyrkouli et al, 1990).…”

Section: Neuropeptides With a Positive Feedback Relationship To Almentioning

confidence: 99%

Hypothalamic neuropeptide signaling in alcohol addiction

Barson

Leibowitz

2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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The hypothalamus is now known to regulate alcohol intake in addition to its established role in food intake, in part through neuromodulatory neurochemicals termed neuropeptides. Certain orexigenic neuropeptides act in the hypothalamus to promote alcohol drinking, although they affect different aspects of the drinking response. These neuropeptides, which include galanin, the endogenous opioid enkephalin, and orexin/hypocretin, appear to stimulate alcohol intake not only through mechanisms that promote food intake but also by enhancing reward and reinforcement from alcohol. Moreover, these neuropeptides participate in a positive feedback relationship with alcohol, whereby they are upregulated by alcohol intake to promote even further consumption. They contrast with other orexigenic neuropeptides, such as melanin-concentrating hormone and neuropeptide Y, which promote alcohol intake under limited circumstances, are not consistently stimulated by alcohol, and do not enhance reward. They also contrast with neuropeptides that can be anorexigenic, including the endogenous opioid dynorphin, corticotropin-releasing factor, and melanocortins, which act in the hypothalamus to inhibit alcohol drinking as well as reward and therefore counter the ingestive drive promoted by orexigenic neuropeptides. Thus, while multiple hypothalamic neuropeptides may work together to regulate different aspects of the alcohol drinking response, excessive signaling from orexigenic neuropeptides or inadequate signaling from anorexigenic neuropeptides can therefore allow alcohol drinking to become dysregulated.

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“…Galanin is a neuropeptide that has been linked to appetitive and consummatory behaviors, including drinking alcohol, via dopamine stimulation in the VS [73, 74]. Nikolova et al [75••] tested the association between VS reactivity and a common functional haplotype (GAL5.1) of a gene coding for galanin ( GAL ) in 138 college students (mean age 19.8 years) using a number-guessing paradigm.…”

Section: Reward Sensitivitymentioning

confidence: 99%

Neuroimaging Risk Markers for Substance Abuse: Recent Findings on Inhibitory Control and Reward System Functioning

et al. 2015

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Rates of alcohol and other drug use rise sharply throughout adolescence and peak in the early 20s. Likewise, prevalence of first-time substance use disorder (SUD) and past-year SUD both peak between ages 18–23. SUD is associated with a host of negative outcomes and is a serious health concern. Understanding the mechanisms that precede the onset and escalation of substance use is crucial in order to develop more effective prevention and intervention strategies for children and adolescents at risk for SUD. In this review, we discuss recent findings from functional neuroimaging studies in children, adolescents, and emerging adults that focus on uncovering the neural underpinnings of SUD risk. The focus is on inhibitory control and reward circuitry due to their involvement in risk-taking behaviors, which are heightened in adolescence and may facilitate substance use. We discuss convergences in the literature and highlight findings suggesting that the association between SUD risk and neurofunctioning may be moderated by age, gender, and history of substance use. Recommendations for future directions are also discussed.

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Ethanol intake is increased by injection of galanin in the paraventricular nucleus and reduced by a galanin antagonist

Cited by 46 publications

References 39 publications

Opioids in the Hypothalamic Paraventricular Nucleus Stimulate Ethanol Intake

Opioids in the Hypothalamic Paraventricular Nucleus Stimulate Ethanol Intake

Hypothalamic neuropeptide signaling in alcohol addiction

Neuroimaging Risk Markers for Substance Abuse: Recent Findings on Inhibitory Control and Reward System Functioning

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