I have read social media articles about caffeine and how it is the most commonly used psychostimulant in the world. Studies have shown a positive correlation between caffeine intake and risky behaviors in young adults. I found a study that examines the long-term effects of caffeine on the behavioral and neurobiological systems of the body. It is known that caffeine intake leads to the non-selective blockade of adenosine A1 and A2A receptors in the nucleus accumbens and caudate-putamen. The blockade of adenosine receptors stimulate the dopamine system, which leads to the release of dopamine. The goal of the study was to determine whether adolescents respond differently to caffeine compared with adults and whether they exhibit greater brain changes associated with chronic caffeine consumption.     

For methodology, male sprague-Dawley rats were given caffeine and quinpirole, which is dopamine D2 receptor agonist. All drugs except caffeine were dissolved in sterile-filtered physiological saline. Caffeine was dissolved in tap water. All rats were the same age. Rats were tested from postnatal to adulthood. They were given a single bottle containing caffeine in water for 28 days. Then, caffeine solution was replaced with water for the remainder at least a week. To test for locomotor activity, rats underwent habituation to the locomotor chambers for 2 hours and on the following day, researchers tested whether cocaine or quinpirole induced more locomotion. Place conditioning preference began 7 days following caffeine consumption. To measure sucrose preference, rats were habituated to drink water from two bottles for 3 days. Then one of the bottles was replaced with sucrose and the total consumption and a preference ratio were used for analysis. Two-bottle choice paradigm was used to test sucrose preferences. To adduce dopamine microdialysis, unilateral microdialysis cannula was implanted under halothane anesthesia into either the right or left NAc shell. Testing began a week later.  

The first result showed a significant increase in caffeine fluid consumption and body weight during the procedure for adolescent and adult rats (Fig 1). Second, adolescent caffeine consumption increased locomotion to cocaine in adulthood (Fig 2). However, caffeine consumption in adults did not influence subsequent cocaine induced locomotor sensitivity and did not develop cocaine-induced conditioned place preference for cocaine in comparison to adolescence (Fig 2b,d). Adolescent caffeine consumption increased locomotor activity at 1mg/kg quinpirole while adult rats did not show any changes in D2 receptor sensitivity (Fig 2f). Third, caffeine consumption during adolescence lowered basal dopamine levels and increased cocaine-induced dopamine release in nucleus accumbens (Fig 3). Fourth, protein expression was measured 7 days following removal of caffeine to investigate the effects of chronic caffeine consumption during adolescence on adenosine and dopamine signaling in the NAc. The results showed a significant increase in adenosine A1 receptor expression and a decrease in adenosine A2A receptor expression in the NAc of animals that consumed caffeine during adolescence. Quinpirole expression was not altered in the NAc in comparison with water controls (Fig 4b). Furthermore, caffeine consumption during adolescence increased DAT (dopamine transport) expression but did not change TH (tyrosine hydroxylase) expression in the NAc. In conclusion, this study proves that adolescent caffeine exposure increases sensitivity to cocaine-induced locomotion. Also, it shows increased adenosine A1 receptor expression and decreased adenosine A2A receptor expression in the NAc in response to caffeine. No behavioral or neurobiologiolcal alterations were seen in adult animals, which shows that the developmental period of adolescence is sensitive to caffeine’s effects on DA signaling in the NAc.

References

O’Neill, C., et al. “Effects of Adolescent Caffeine Consumption on Cocaine Sensitivity.” Nature News, Nature Publishing Group, 20 October 2014.