Long-term behavioral programming induced by peripuberty stress in rats is accompanied by GABAergic-related alterations in the Amygdala

PLoS One. 2014 Apr 15;9(4):e94666. doi: 10.1371/journal.pone.0094666. eCollection 2014.

Abstract

Stress during childhood and adolescence is a risk factor for psychopathology. Alterations in γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain, have been found following stress exposure and fear experiences and are often implicated in anxiety and mood disorders. Abnormal amygdala functioning has also been detected following stress exposure and is also implicated in anxiety and social disorders. However, the amygdala is not a unitary structure; it includes several nuclei with different functions and little is known on the potential differences the impact of early life stress may have on this system within different amygdaloid nuclei. We aimed here to evaluate potential regional differences in the expression of GABAergic-related markers across several amygdaloid nuclei in adult rats subjected to a peripuberty stress protocol that leads to enhanced basal amygdala activity and psychopathological behaviors. More specifically, we investigated the protein expression levels of glutamic acid decarboxylase (GAD; the principal synthesizing enzyme of GABA) and of GABA-A receptor subunits α2 and α3. We found reduced GAD and GABA-A α3, but not α2, subunit protein levels throughout all the amygdala nuclei examined (lateral, basolateral, basomedial, medial and central) and increased anxiety-like behaviors and reduced sociability in peripubertally stressed animals. Our results identify an enduring inhibition of the GABAergic system across the amygdala following exposure to early adversity. They also highlight the suitability of the peripuberty stress model to investigate the link between treatments targeting the dysfunctional GABAergic system in specific amygdala nuclei and recovery of specific stress-induced behavioral dysfunctions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / metabolism*
  • Animals
  • Anxiety / psychology
  • Behavior, Animal*
  • Body Weight
  • Exploratory Behavior
  • Glutamate Decarboxylase / metabolism
  • Interpersonal Relations
  • Puberty / metabolism
  • Puberty / psychology*
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / metabolism
  • Stress, Psychological / metabolism*
  • Stress, Psychological / psychology
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Gabra2 protein, rat
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid
  • Glutamate Decarboxylase

Grant support

This work was supported by grants from the Swiss National Science Foundation (31003AB-135710 and the NCCR Synapsy), Oak Foundation, and intramural funding from the EPFL, as well as by the Spanish Ministry of Economy and Competitiveness BFU2012-32512, MICINN-PIM2010ERN 00577/NEUCONNECT in the frame of ERA-NET NEURON, Generalitat Valenciana ACOMP/2012/229 and Prometeo Excellence Program PROMETEO2013/069 and the Fundación Alicia Koplowitz. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.