Effects of Adolescent Caffeine Consumption on Cocaine Sensitivity

Abstract

Caffeine is the most commonly used psychoactive substance, and consumption by adolescents has risen markedly in recent years. We identified the effects of adolescent caffeine consumption on cocaine sensitivity and determined neurobiological changes within the nucleus accumbens (NAc) that may underlie caffeine-induced hypersensitivity to cocaine. Male Sprague-Dawley rats consumed caffeine (0.3 g/l) or water for 28 days during adolescence (postnatal day 28-55; P28-P55) or adulthood (P67-P94). Testing occurred in the absence of caffeine during adulthood (P62-82 or P101-121). Cocaine-induced and quinpirole (D 2 receptor agonist)-induced locomotion was enhanced in rats that consumed caffeine during adolescence. Adolescent consumption of caffeine also enhanced the development of a conditioned place preference at a sub-threshold dose of cocaine (7.5 mg/kg, i.p.). These behavioral changes were not observed in adults consuming caffeine for an equivalent period of time. Sucrose preferences were not altered in rats that consumed caffeine during adolescence, suggesting there are no differences in natural reward. Caffeine consumption during adolescence reduced basal dopamine levels and augmented dopamine release in the NAc in response to cocaine (5 mg/kg, i.p.). Caffeine consumption during adolescence also increased the expression of the dopamine D 2 receptor, dopamine transporter, and adenosine A 1 receptor and decreased adenosine A 2A receptor expression in the NAc. Consumption of caffeine during adulthood increased adenosine A 1 receptor expression in the NAc, but no other protein expression changes were observed. Together these findings suggest that caffeine consumption during adolescence produced changes in the NAc that are evident in adulthood and may contribute to increases in cocaine-mediated behaviors.

Adolescent caffeine consumption increases adulthood anxiety-related behavior and modifies neuroendocrine signaling

“…Analogous consumption data (not shown) were collected for each cohort of adolescent and adult rats that were used to examine anxiety behaviors. No significant group differences were detected in any of the cohorts and all data is comparable to previously published results using this procedure (O’Neill et al, 2015). …”

“…A two-way ANOVA revealed a significant main effect of stress (F 1,26 = 87.86, p< 0.0001), but no main effect of treatment or treatment X stress interaction. Although the nucleus accumbens (NAc) shell is not typically examined in stress-related studies, we have previously shown alterations in the expression of several proteins within the NAc shell following exposure to caffeine during adolescence (O’Neill et al, 2015). A two-way ANOVA revealed a main effect of stress (F 1,26 = 80.26, p< 0.0001), but no significant treatment X stress interaction or main effect of treatment (Figure 5F).…”

“…Seven days after arrival, caffeine-consuming rats were given access to a single bottle containing caffeine in water (0.3 g/L) for 28 days based on previously published procedures (Ardais et al, 2014; O’Neill et al, 2015). Caffeine consumption procedures occurred continuously between P28-P55 in adolescent studies and P67-94 in adult studies.…”

Trajectories of energy drink consumption and subsequent drug use during young adulthood

“…ED consumption might have a unique contributory role for the development and escalation of NPS and cocaine use among young adults. Interestingly, animal studies have supported the notion that caffeine can enhance the reinforcing effects and motivational value of cocaine, especially when co-ingested (O’Neill et al, 2015; Prieto et al, 2016). Earlier research showed an association between caffeine administration and dose-dependent increases in self-administration of stimulants (Schenk et al, 1996).…”

“…Laboratory studies have shown that caffeine enhances nicotine’s reinforcing and analgesic effects and potentiates the addictive properties of other stimulant drugs (Jones and Griffiths, 2003; O’Neill et al, 2015; Sigmon and Griffiths, 2011; Tanda and Goldberg, 2000). Furthermore, the rapid-onset stimulant effects of EDs—especially among younger consumers who have not yet developed tolerance to caffeine—might provoke some consumers to seek out similar or even more intense effects via other drugs (Reissig et al, 2009).…”