Nutritional Contingency Reduces Alcohol Drinking by Altering Central Neurotransmitter Receptor Gene Expression in Rats

Abstract

We have previously shown that 6 weeks of intermittent high-fat diet (Int-HFD) pre-exposure significantly reduced alcohol drinking in rats, providing preliminary evidence of the effectiveness of a dietary intervention in reducing alcohol intake. However, the functional framework and underlying neurobiological mechanisms of such dietary intervention are unknown. Here, we examined the impact of Int-HFD pre-exposure duration on alcohol drinking, plasma feeding peptides, and central neurotransmitter receptors gene expression. Male Long Evans rats (n = 6–7/group) received no pre-exposure, 1 or 2 weeks pre-exposure to Int-HFD and alcohol drinking (two-bottle choice) was evaluated. We observed HFD pre-exposure-dependent decrease in alcohol drinking, with a significant decrease observed following 2 weeks of Int-HFD pre-exposure. No significant between-group differences in plasma feeding peptides (i.e., ghrelin, leptin, insulin) were detected. A PCR array revealed that the expression of several neurotransmitter receptors was significantly (p < 0.05 and ≥2-fold) altered in the striatum and ventral tegmental area compared to controls. These data suggest that pre-exposure to a palatable diet is critical to reduce alcohol drinking in rats, possibly through genetic alterations in the brain reward circuitry. Importantly, the present study is a step forward in identifying the critical framework needed to evaluate the therapeutic potential of nutritional contingency in the management of alcoholism.

Behavioral and Neurobiological Consequences of Hedonic Feeding on Alcohol Drinking

“…Again alcohol drinking was significantly reduced in the intermittent HFD exposed group of rats compared to the chow controls [54]. Using the similar paradigm, a more recent study from our lab has identified that intermittent HFD pre-exposure is critical to reducing alcohol drinking [55]. It is important to mention here that our studies utilized male adult rats, and it is unclear if similar results could be obtained in female rats.…”

“…A recent study found no differences in the plasma feeding peptides in rats displaying reduced alcohol drinking phenotype following a binge/compensate HFD feeding [55]. In addition, gene expression of several neurotransmitter receptors was significantly altered in the striatum and VTA of rats displaying binge/compensate HFD feeding compared to the chow controls, whereas no such changes were observed in the amygdala and hypothalamus [55]. These data collectively argue against the involvement of peripheral systems and point towards central mechanisms, particularly brain reward regions, in mediating reduced alcohol drinking following binge-like HFD intake.…”

“…To summarize, reduced alcohol intake in binge-exposed rats could derive from multiple mechanisms, including physiological and neurobiological processes linked to control both food and alcohol intake. A recent study found no differences in the plasma feeding peptides in rats displaying reduced alcohol drinking phenotype following a binge/compensate HFD feeding [55]. In addition, gene expression of several neurotransmitter receptors was significantly altered in the striatum and VTA of rats displaying binge/compensate HFD feeding compared to the chow controls, whereas no such changes were observed in the amygdala and hypothalamus [55].…”

Evidence for Modulation of Substance Use Disorders by the Gut Microbiome: Hidden in Plain Sight

“…However, intermittent exposure to an HFD for 6 to 7 weeks can either decrease (Sirohi et al, 2017) or increase (Coker et al, 2020) alcohol drinking, so it appears that additional variables are operational. Data from the studies discussed above supported the conclusion that the observed outcomes were attributed to alterations in neurotransmitter neurochemistry (Peleg-Raibstein et al, 2016;Villavasso et al, 2019), decreased anxiety and elevated ghrelin (Sirohi et al, 2017), and the development of insulin insensitivity and glucose intolerance (Coker et al, 2020).…”

“…Offspring from dams exposed to an HFD throughout pregnancy and lactation showed increased alcohol drinking in adulthood (Peleg-Raibstein et al, 2016). Adult rats given access to an HFD on an intermittent schedule significantly decreased their alcohol drinking (Sirohi et al, 2017;Villavasso et al, 2019). Coker et al (2020) carried out an extensive analysis of the impact of HFD access schedules on alcohol drinking, and the results were very interesting.…”