title: 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 (D2 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 D2 receptor, dopamine transporter, and adenosine A1 receptor and decreased adenosine A2A receptor expression in the NAc. Consumption of caffeine during adulthood increased adenosine A1 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.
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, USA.
authors.forename: Casey E
authors.initials: CE
authors.lastname: O'Neill
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, USA.
authors.forename: Sophia C
authors.initials: SC
authors.lastname: Levis
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, USA.
authors.forename: Drew C
authors.initials: DC
authors.lastname: Schreiner
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Amat
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, USA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Maier
authors.affiliation: 1] Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, USA [2] Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Bachtell
mesh_terms: D000367:Age Factors; D000818:Animals; D002110:Caffeine / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D005518:Food Preferences / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043683:Receptors, Adenosine A2 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D043682:Receptor, Adenosine A1; D043683:Receptors, Adenosine A2; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D002110:Caffeine; D003042:Cocaine; D004298:Dopamine