Effect of Ethanol on Hypothalamic Opioid Peptides, Enkephalin, and Dynorphin: Relationship With Circulating Triglycerides

Abstract

Background: Recent evidence has demonstrated that ethanol intake can stimulate the expression and production of the feeding-stimulatory peptide, galanin (GAL), in the hypothalamic paraventricular nucleus (PVN), and that PVN injection of this peptide, in turn, can increase the consumption of ethanol. To test the hypothesis that other feeding-related systems are involved in ethanol intake, this study examined the effect of ethanol on the hypothalamic opioid peptides, enkephalin (ENK), and dynorphin (DYN).Method: Adult, male Sprague-Dawley rats were trained to voluntarily drink increasing concentrations of ethanol, up to 9% v/v, on a 12-hour access schedule or were given a single injection of ethanol (10% v/v) versus saline vehicle. The effect of ethanol on GAL, ENK, and DYN mRNA was measured using real-time quantitative polymerase chain reaction and radiolabeled in situ hybridization, while radioimmunoassay was used to measure peptide levels. In addition to blood alcohol, circulating levels of triglycerides (TG), leptin, and insulin were also measured.Results: The data demonstrated that: (1) rats voluntarily drinking 9% v/v ethanol (approximately 2.0 g/kg/d) show a significant increase in GAL, ENK, and DYN mRNA in the PVN compared with water-drinking rats; (2) voluntary consumption of ethanol also increases peptide levels of ENK and DYN in the PVN; (3) acute injection of 10% ethanol (1.0 g/kg of 10% v/v) similarly increases the expression of GAL, ENK, and DYN in the PVN; and (4) ethanol consumption and injection, while having little effect on leptin and insulin, consistently increase circulating levels of TG as well as alcohol, both of which are strongly, positively correlated with peptide expression in the PVN.Conclusions: These findings, together with published studies, suggest a possible role for hypothalamic opioid peptides in the drinking of ethanol. Based on evidence that dietary fat and lipid injections stimulate the PVN peptides and injection of the opiates and GAL increase ethanol intake, it is proposed that both TG and alcohol in the circulation, which are elevated by the ingestion or injection of ethanol, are involved in stimulating these peptides in the PVN, which in turn promote further consumption of ethanol.

Overconsumption of dietary fat and alcohol: Mechanisms involving lipids and hypothalamic peptides

“…While earlier studies of endogenous opioids in whole hypothalamus yielded mixed results, ENK mRNA in the PVN was shown to be significantly stimulated after 24 hours by acute intragastric infusion of 30% ethanol [60], while unaffected by intake of 5% ethanol [61]. In a recent report [62], a strong, stimulatory effect of ethanol on PVN opioids has been described. Rats voluntarily drinking 9% ethanol (1.0-2.5 g/kg/day) show a significant increase in expression of both ENK and DYN in the PVN, similar to that seen with GAL.…”

“…There is evidence that ethanol like dietary fat can increase circulating levels of TG [35,62,63]. The injection as well as consumption of ethanol in rats consistently increases circulating levels of TG, together with blood levels of alcohol [62].…”

The International Society for Developmental Psychobiology 39th Annual Meeting Symposium: Alcohol and Development: Beyond fetal alcohol syndrome

“…Enkephalin and dynorphin concentrations along with galanin, were found to be increased in the PVN with injection and consumption of alcohol (Chang et al, 2007). Like galanin, both of these endogenous opioids increase food intake.…”

“…They found that in rats trained to prefer alcohol over water for many weeks, microinjection of this 29-30 amino acid peptide into the third ventricle near the paraventricular nucleus (PVN) (Lewis et al) or in the nucleus itself (Rada, Avena, Leibowitz, & Hoebel, 2004) increased alcohol intake. Furthermore, it has been recently observed that administration of alcohol increases galanin expression in the hypothalamus (Chang et al, 2007). In rats that had been consuming alcohol for 6 or more weeks, galanin did not increase the consumption of their chow diet.…”

Effects of a single high dose of Chlorpyrifos in long-term feeding, ethanol consumption and ethanol preference in male Wistar rats with a previous history of continued ethanol drinking

“…Besides, levels of orexin mRNA (Morgansterm et al et al, 2010) were reduced and levels of opioid encephalin and galanin were increased (Chang et al, 2007 by chronic exposure to ethanol.…”