Predictors of ethanol consumption in adult Sprague–Dawley rats: relation to hypothalamic peptides that stimulate ethanol intake

Abstract

To investigate mechanisms in outbred animals that increase propensity to consume ethanol, it is important to identify and characterize these animals before or at early stages in their exposure to ethanol. In the present study, different measures were examined in adult, Sprague-Dawley rats to determine whether they can predict long-term propensity to over-consume ethanol. Prior to consuming 9% ethanol with a two-bottle choice paradigm, rats were examined with the commonly-used behavioral measures of novelty-induced locomotor activity and anxiety, as assessed during 15 min in an open field activity chamber. Two additional measures, intake of a low 2% ethanol concentration or circulating triglyceride levels after a meal, were also examined with respect to their ability to predict chronic 9% ethanol consumption. The results revealed significant positive correlations across individual rats between the amount of 9% ethanol ultimately consumed and three of these different measures, with high scores for activity, 2% ethanol intake, and triglycerides identifying rats that consume 150% more ethanol than rats with low scores. Measurements of hypothalamic peptides that stimulate ethanol intake suggest that they contribute early to the greater ethanol consumption predicted by these high scores. Rats with high 2% ethanol intake or high triglycerides, two measures found to be closely related, had significantly elevated expression of enkephalin and galanin in the hypothalamic paraventricular nucleus (PVN) but no change in neuropeptide Y in the arcuate nucleus (ARC). This is in contrast to rats with high activity scores, which in addition to elevated PVN enkephalin expression showed enhanced neuropeptide Y in the ARC but no change in galanin. Whereas elevated enkephalin is a common characteristic related to all three predictors of chronic ethanol intake, the other peptides differentiate these predictors, with galanin enhanced with high 2% ethanol intake and triglyceride measures but neuropeptide Y related to activity.

Neurobiology of Consummatory Behavior: Mechanisms Underlying Overeating and Drug Use

“…One popular technique used to elicit voluntary drinking, known as “sucrose fading”, involves initially mixing ethanol with sucrose for training purposes and then slowly reducing the sucrose concentration and escalating the ethanol concentration until animals show stable drinking (Samson 1986). Another technique is to start animals on a very low ethanol concentration and then slowly increase this every few days until the desired concentration is reached (Karatayev et al 2010a; Morganstern et al 2010a; Sandbak and Murison 1996). Both of these methods give the animal a choice between an ethanol solution and water.…”

“…Further, single measures of locomotor activity and also of circulating triglycerides (TG) levels after a fat-rich meal are closely related to and found to predict caloric intake of chronically available high-fat diet in SD rats (Karatayev et al 2009b; Morganstern et al 2010c). Most interesting is the finding that these measures of activity and TG are similarly found to predict long-term patterns of ethanol drinking, as well as lever-pressing for ethanol (Karatayev et al 2010a; Nadal et al 2002). Additionally, the consumption of a sweet saccharin solution or a low 2% ethanol solution for just a few days can successfully predict long-term patterns of ethanol self-administration (Karatayev et al 2010a; Koros et al 1998).…”

“…Most interesting is the finding that these measures of activity and TG are similarly found to predict long-term patterns of ethanol drinking, as well as lever-pressing for ethanol (Karatayev et al 2010a; Nadal et al 2002). Additionally, the consumption of a sweet saccharin solution or a low 2% ethanol solution for just a few days can successfully predict long-term patterns of ethanol self-administration (Karatayev et al 2010a; Koros et al 1998). Interestingly, the previously discussed alcohol-preferring P rats in addition to several other rat lines and mouse strains (e.g.…”

Amygdalar neuronal plasticity and the interactions of alcohol, sex, and stress

“…ENK is known to be involved in the rewarding actions of alcohol (Tseng et al 2013), and it may play a role in promoting and stimulating intake (Chang et al 2010). In support of this, an acute dose of ethanol was shown to increase c-Fos immunoreactivity in ENK neurons of the CeA, and high levels of ENK is a predictor of increased alcohol consumption (Karatayev et al 2010; Criado and Morales 2000). …”

Common effects of fat, ethanol, and nicotine on enkephalin in discrete areas of the brain

“…There is evidence that lipids can contribute to the stimulation of ENK gene expression, as indicated in studies showing ENK mRNA in the PVN to be increased by acute injection of Intralipid or by the fatty acid linoleic acid and also by the consumption of a fat-rich meal (Oomura et al, 1975; Chang et al, 2004; Chang et al, 2007). This elevated PVN ENK may, in turn, further stimulate consummatory behavior, as shown in rats that have spontaneously high post-meal TG (Karatayev et al, 2009) and subsequently eat more fat and drink more ethanol when offered these substances (Karatayev et al, 2009; Karatayev et al, 2010). Although further studies are needed to characterize the mechanisms mediating the stimulatory effect of lipids on ENK, there is evidence showing that lipids can alter, either directly or indirectly, a variety of central neural processes.…”