Differential consumption of alcohol, caffeine, and caffeinated alcohol by adolescent rats, and effects on post-adolescent gene expression signatures in the nucleus accumbens and orbitofrontal cortex

Drug Alcohol Depend. 2023 Oct 1:251:110921. doi: 10.1016/j.drugalcdep.2023.110921. Epub 2023 Aug 7.

Abstract

Caffeinated alcoholic beverages (CABs) are widely consumed despite little known about their behavioral and biological effects. Furthermore, CABs are also popular among adolescents, a particularly vulnerable and maturing demographic. In this preliminary study, we compared levels of daily adolescent voluntary consumption of caffeine (0.03%), alcohol (10%), caffeinated alcohol (0.03% + 10%), or vehicle and evaluated the effects of this on mRNA expression in brain regions associated with addiction and known to be affected by each drug. Beginning on postnatal day 30, rats were allowed unrestricted access to gelatin combined with one, both, or neither drug for twenty days. Compared to vehicle-consuming animals, consumption of gelatin was significantly attenuated when alcohol was included. The addition of caffeine to alcohol increased alcohol consumption in the early days of access compared to alcohol alone; however, after two weeks, alcohol consumption between these groups reached comparable levels. Compared to animals consuming caffeine alone, combining caffeine with alcohol significantly reduced caffeine intake. Targeted mRNA analysis of tissue collected from the nucleus accumbens and orbitofrontal cortex after the consumption period identified unique patterns of differentially expressed genes between treatment groups, across a broad array of neurotransmitter systems. Of particular note were genes related to a number of solute transporters and serotonergic functions. This preliminary work suggests unique pharmacological and behavioral effects from consuming caffeinated alcohol during adolescence. Since CABs are widely consumed by adolescents, these results suggest that more research into the pharmacological and behavioral effects elicited by CABs is warranted.

Keywords: Adolescent; Alcohol; Caffeine; TREx; TruSeq targeted RNA expression.