Elsevier

Neuroscience

Volume 148, Issue 3, 7 September 2007, Pages 794-805
Neuroscience

Systems neuroscience
Exposure to novelty and forced swimming evoke stressor-dependent changes in extracellular GABA in the rat hippocampus

https://doi.org/10.1016/j.neuroscience.2007.06.030Get rights and content

Abstract

In the hippocampus, a brain structure critically important in the stress response, GABA controls neuronal activity not only via synaptic inhibition, but also via tonic inhibition through stimulation of extrasynaptic GABA receptors. The extracellular level of GABA may represent a major determinant for tonic inhibition and, therefore, it is surprising that its responsiveness to stress has hardly been investigated. To clarify whether hippocampal extracellular GABA levels change in response to acute stress, we conducted an in vivo microdialysis study in rats. We found that dialysate GABA levels respond to various neuropharmacological manipulations such as reuptake inhibition, elevated concentrations of K+, tetrodotoxin and baclofen, indicating that a large proportion of hippocampal extracellular GABA depends on neuronal release and that GABA re-uptake plays a role in determining the extracellular levels of this neurotransmitter. Next, rats were exposed to a novel cage or to forced swimming in 25 °C water. Interestingly, these two stressors resulted in opposite effects. Novelty caused a fast increase in GABA (120% of baseline), whereas forced swimming resulted in a profound decrease (70% of baseline). To discriminate between the psychological and physical aspects (i.e. the effects on body temperature) of forced swimming, another group of animals was forced to swim at 35 °C. This stressor, like novelty, caused an increase in hippocampal GABA, suggesting a stimulatory effect of psychological stress. The effects of novelty could not be blocked by the corticotropin-releasing factor receptor antagonist D-Phe-CRF12-41. These results are the first to demonstrate stressor-dependent changes in hippocampal extracellular GABA; an observation which may be of particular significance for GABAergic tonic inhibition of hippocampal neurons.

Section snippets

Animals

Male Wistar rats (breeding stock University of Bristol) were housed three per cage under standard housing conditions (lights on from 05:00–19:00 h; temperature 21–22 °C; relative humidity 40–60%; free access to food pellets and drinking water). At the time of surgery, the body weight of the rats was about 220 g. Rats were handled once per day (5 min per rat) starting 1 week before surgery to allow them to familiarise to the experimenter and the i.c.v. injection procedure and was continued after

Pharmacological characterization of hippocampal extracellular levels of GABA as measured by in vivo microdialysis

Fig. 1 shows an example of a chromatogram of GABA in a standard and of GABA in a dialysate sample. Mean basal levels of extracellular GABA were 373.0±16.2 fmol/10 min sample (n=61), not corrected for the recovery of the dialysis membrane. There was no significant correlation between hippocampal extracellular levels of GABA and behavioural activity under baseline (i.e. non-stress conditions; r=0.062, P>0.05). Perfusion of the probe with Ringer solution containing a high concentration of

Discussion

The data presented here are the first to demonstrate that extracellular GABA in the hippocampus responds to stress in a stressor-dependent manner. Novel cage exposure, a mild psychological stressor, increased hippocampal GABA levels. In contrast, forced swimming in 25 °C water, a stressor with combined physical and psychological aspects, resulted in a profound decrease in extracellular GABA in this brain structure. When the physical impact of forced swimming was limited by using 35 °C water,

Conclusion

In summary, these data demonstrate for the first time rapid and stressor-specific changes in extracellular GABA in the hippocampus of the rat, that seem to be independent of CRF. These data are of particular significance for the study of tonic inhibition by GABA in the hippocampus as they show that changes in the extracellular concentrations of this neurotransmitter, probably a key determinant for the degree of tonic inhibition, occur under physiologically relevant circumstances like stress. As

Acknowledgments

Supported by the Neuroendocrinology Charitable Trust grant PMS/MMS-02/03/884.

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