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

Psychoneuroendocrinology. 2016 May;67:40-50. doi: 10.1016/j.psyneuen.2016.01.030. Epub 2016 Feb 1.


Caffeine is a commonly used psychoactive substance and consumption by children and adolescents continues to rise. Here, we examine the lasting effects of adolescent caffeine consumption on anxiety-related behaviors and several neuroendocrine measures in adulthood. Adolescent male Sprague-Dawley rats consumed caffeine (0.3g/L) for 28 consecutive days from postnatal day 28 (P28) to P55. Age-matched control rats consumed water. Behavioral testing for anxiety-related behavior began in adulthood (P62) 7 days after removal of caffeine. Adolescent caffeine consumption enhanced anxiety-related behavior in an open field, social interaction test, and elevated plus maze. Similar caffeine consumption in adult rats did not alter anxiety-related behavior after caffeine removal. Characterization of neuroendocrine measures was next assessed to determine whether the changes in anxiety were associated with modifications in the HPA axis. Blood plasma levels of corticosterone (CORT) were assessed throughout the caffeine consumption procedure in adolescent rats. Adolescent caffeine consumption elevated plasma CORT 24h after initiation of caffeine consumption that normalized over the course of the 28-day consumption procedure. CORT levels were also elevated 24h after caffeine removal and remained elevated for 7 days. Despite elevated basal CORT in adult rats that consumed caffeine during adolescence, the adrenocorticotropic hormone (ACTH) and CORT response to placement on an elevated pedestal (a mild stressor) was significantly blunted. Lastly, we assessed changes in basal and stress-induced c-fos and corticotropin-releasing factor (Crf) mRNA expression in brain tissue collected at 7 days withdrawal from adolescent caffeine. Adolescent caffeine consumption increased basal c-fos mRNA in the paraventricular nucleus of the hypothalamus. Adolescent caffeine consumption had no other effects on the basal or stress-induced c-fos mRNA changes. Caffeine consumption during adolescence increased basal Crf mRNA in the central nucleus of the amygdala, but no additional effects of stress or caffeine consumption were observed in other brain regions. Together these findings suggest that adolescent caffeine consumption may increase vulnerability to psychiatric disorders including anxiety-related disorders, and this vulnerability may result from dysregulation of the neuroendocrine stress response system.

Keywords: Adolescence; Corticotropin-releasing hormone; Glucocorticoid; Hypothalamic–pituitary–adrenal axis; Immediate early gene.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Aging / blood
  • Aging / metabolism
  • Aging / psychology*
  • Amygdala / drug effects
  • Amygdala / metabolism
  • Animals
  • Anxiety / blood
  • Anxiety / chemically induced*
  • Anxiety / metabolism
  • Behavior, Animal / drug effects
  • Caffeine / pharmacology*
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / biosynthesis
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Male
  • Paraventricular Hypothalamic Nucleus / drug effects
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / physiopathology
  • Rats
  • Stress, Psychological / blood
  • Stress, Psychological / chemically induced
  • Stress, Psychological / metabolism


  • Caffeine
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Corticosterone