Hypothalamic neuropeptide signaling in alcohol addiction

Abstract

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.

Intermittent access to a nutritionally complete high-fat diet attenuates alcohol drinking in rats

“…Utilizing this limited access (2hr) paradigm, we have recently shown that binge-like intake of high fat diet (HFD) induced anxiolytic effects and attenuated alcohol consumption in non-dependent rats (Sirohi et al, 2016). This finding could be explained by the length and exposure history of a calorie-rich food, which has fundamentally different behavioral outcomes (Krishna et al, 2016; Tracy et al, 2015) or changes in the feeding peptides, which control behavioral constructs such as motivation and anxiety that also contribute to excess alcohol intake (Barson and Leibowitz, 2016; Morganstern et al, 2011). Therefore, in the present study, we hypothesized that extended intermittent access to HFD would lead to increased alcohol consumption in non-dependent rodents.…”

Orexin-1 receptor blockade suppresses compulsive-like alcohol drinking in mice

“…Over the years, OX – a neuropeptide synthesized in a subgroup of lateral hypothalamic cells which have projections throughout the brain – has been identified to play a role in a number of homeostatic and regulatory behaviors, including feeding, sleep-wake cycle, as well as emotional and neuroendocrine regulation (Brown et al, 2015a; Li et al, 2016; Mahler et al, 2014). OXRs have also been addressed in many studies of drugs of abuse, including cocaine, opioids, nicotine and alcohol (Barson and Leibowitz, 2016; Boutrel et al, 2013; Mahler et al, 2014; Mahler et al, 2012). There are two subtypes of OX receptors, OX1R and OX2R (Mahler et al, 2012).…”

GAL3 receptor knockout mice exhibit an alcohol‐preferring phenotype

“…). The paraventricular nucleus in particular has been implicated in the relationship between GAL and fat intake (Barson & Leibowitz ). Alcohol is the only drug of abuse that has a caloric content, and the consumption of alcohol results in an increase in circulating lipids as seen in HFDs (Chang et al .…”