Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice

Abstract

The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61) exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations.

A review of the addiction potential of energy drink-alcohol mix

“…Multiple studies have found that caffeine can possibly reduce one's ability to accurately assess the intoxicating effects of alcohol [15][16][17][18][19]. Participants who consumed alcohol mixed with energy drinks tend to report subjectively lower intoxication levels compared to those who consumed alcohol alone and with the same estimated blood alcohol concentration (eBAC) [17][18][19].…”

“…A recent study on adolescent mice showed that repeated exposure to caffeine-mixed alcohol resulted in significant locomotor sensitisation, similar to chronic cocaine use [15]. Compared to alcohol or caffeine use alone, increased amounts of protein ΔFosB accumulate in the nucleus accumbens following repeated caffeine-mixed alcohol exposure [15].…”

“…Compared to alcohol or caffeine use alone, increased amounts of protein ΔFosB accumulate in the nucleus accumbens following repeated caffeine-mixed alcohol exposure [15]. The nucleus accumbens is intimately involved in reward associated learning and behaviours, particularly the development of substance use disorders.…”

“…It was found that mice exposed to caffeinemixed alcohol during adolescence were desensitized to substances that give a pleasurable effect such as saccharine and would subsequently consume greater amounts of the substance. This points to altered reward pathways in the brain and desensitization in such a way that humans who are similarly exposed to caffeine-mixed alcohol would have a greater propensity towards substance abuse in adulthood [15].…”

The multiplicative effect of combining alcohol with energy drinks on adolescent gambling

“…Decreased striatal activation during reward processing has been found in gambling disorder, binge-eating, and alcohol dependence (Potenza, 2014). Repeated consumption of caffeine-mixed alcohol causes stronger activation of the dopaminergic reward pathway than caffeine or alcohol alone (Robins, Lu, & van Rijn, 2016). Furthermore, previous studies examining neurobiological correlates of problem gambling have identified abnormalities in brain dopamine systems that are crucial for reward sensitivity (Wardell, Quilty, Hendershot, & Bagby, 2015).…”