Stressor exposure of male and female juvenile mice influences later responses to stressors: modulation of GABAA receptor subunit mRNA expression

Neuroscience. 2012 Jul 26;215:114-26. doi: 10.1016/j.neuroscience.2012.04.038. Epub 2012 Apr 25.


Stressors encountered during the juvenile period may have persistent effects on later behavioral and neurochemical functioning and may influence later responses to stressors. In the current investigation, we evaluated the influence of stressor exposure applied during the juvenile period (26-28 days of age) on anxiety-related behavior, plasma corticosterone and on GABA(A) α2, α3, α5 and γ2 mRNA expression within the prefrontal cortex (PFC) and amygdala measured during adulthood. These changes were monitored in the absence of a further challenge, as well as in response to either a social or a non-social psychogenic stressor administered during adulthood. Exposure to an acute adult stressor elicited anxiety in females and was still more pronounced among females that had also experienced the juvenile stressor. Among males, arousal and impulsivity predominated so that anxiety responses were less notable. Furthermore, experiencing the stressor as a juvenile influenced adult GABA(A) subunit expression, as did the adult stressor experience. These changes were differentially expressed in males and females. Moreover, these subunit variations were further moderated among mice that stressed as juveniles and were again exposed to an adult stressor. Interestingly, under conditions in which the juvenile stressor increased the expression of a particular subunit, exposure to a further stressor in adulthood resulted in the γ-aminobutyric acid (GABA) subunit variations being attenuated in both sexes. The current results suggest that juvenile and adult stressor experiences elicit variations of GABA(A) receptor subunit expression that are region-specific as well as sexually-dimorphic. Stressful events during the juvenile period may have pronounced proactive effects on anxiety-related behaviors, but linking these to specific GABA(A) subunits is made difficult by the diversity of GABA changes that are evident as well as the dimorphic nature of these variations. Nevertheless, these GABA(A) sex-specific subunit variations may be tied to the differences in anxiety in males and females.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Brain / metabolism
  • Brain / pathology
  • Corticosterone / blood
  • Female
  • Gene Expression Regulation, Developmental / physiology*
  • Male
  • Maze Learning / physiology
  • Mice
  • Protein Subunits / genetics*
  • Protein Subunits / metabolism
  • RNA, Messenger / metabolism*
  • Reaction Time / physiology
  • Receptors, GABA-A / genetics*
  • Receptors, GABA-A / metabolism
  • Sex Characteristics*
  • Stress, Psychological / blood
  • Stress, Psychological / complications
  • Stress, Psychological / metabolism*


  • Protein Subunits
  • RNA, Messenger
  • Receptors, GABA-A
  • Corticosterone