Short- and long-term effects of juvenile stressor exposure on the expression of GABA_A receptor subunits in rats

Abstract

During the juvenile period rodents are particularly sensitive to stressors. Aversive events encountered during this period may have enduring effects that are not evident among animals initially stressed as adults. Interestingly, experiencing stressor during juvenile period was found to elicit a biphasic behavioral pattern over the course of development. During the juvenile period, the expression of several GABA_A receptor subunits is subject to elevated plasticity, rendering the GABAergic system sensitive to stressors. In the present investigation, animals were exposed to a juvenile variable stressor regimen (JUV-S) at 27–29 postnatal days (PND): 27 PND—acute swim stress (10 min), 28 PND—elevated platform stress (3 sessions × 30 min each), and 29 PND—restraint (2 h). One hour following the last exposure to stressor or in adulthood (60 PND), anxiety-related behaviors were assessed in a 5-min elevated plus maze test. The western blotting technique was used to evaluate whether the juvenile stress induced behavioral pattern will be accompanied by respective changes in GABA_A α₁, α₂, and α₃ protein expression in male rats. Our findings further established that juvenile stressor elicits hyper-reactivity when rats were tested as juveniles, whereas rats exhibited reduced activity and increased anxiety when tested as adults. Additionally, the effects of juvenile stressor on α₁, α₂, and α₃ were more pronounced among juvenile stressed rats that were challenged as adults compared with rats that were only challenged as juveniles. Interestingly, the stress-induced modulation of the subunits was particularly evident in the amygdala, a brain region closely associated with anxiety. Thus, age- and region-specific alterations of the α subunits may contribute to the age-specific behavioral alterations observed following juvenile stress exposure.

Keywords::

• Amygdala
• anxiety
• elevated plus maze
• GABA_A receptor
• hippocampus
• juvenile stressor

Acknowledgments

We thank Prof. Hymie Anisman for valuable comments on this paper.

Declaration of interest: This work was funded by a Deutsche Israel Project cooperation grant to G.R-L and by a grant from the Institute for the Study of Affective Neuroscience, University of Haifa, which was endowed by the Hope for Depression Research Foundation, to G.R-L. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.