Elsevier

Neuroscience

Volume 163, Issue 1, 29 September 2009, Pages 490-499
Neuroscience

Systems Neuroscience
Research Paper
Pentylenetetrazole-induced seizures affect binding site densities for GABA, glutamate and adenosine receptors in the rat brain

https://doi.org/10.1016/j.neuroscience.2009.03.068Get rights and content

Abstract

Pentylenetetrazole (PTZ) is a convulsant used to model epileptic seizures in rats. In the PTZ-model, altered heat shock protein 27 (HSP-27) expression highlights seizure-affected astrocytes, which play an important role in glutamate and GABA metabolism. This raises the question whether impaired neurotransmitter metabolism leads to an imbalance in neurotransmitter receptor expression. Consequently, we investigated the effects of seizures on the densities of seven different neurotransmitter receptors in rats which were repeatedly treated with PTZ (40 mg/kg) over a period of 14 days. Quantitative in vitro receptor autoradiography was used to measure the regional binding site densities of the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and N-methyl-d-aspartate (NMDA) receptors, the adenosine receptor type 1 (A1), which is part of the system controlling glutamate release, and the γ-aminobutyric acid (GABA) receptors GABAA and GABAB as well as the GABAA-associated benzodiazepine (BZ) binding sites in each rat. Our results demonstrate altered receptor densities in brain regions of PTZ-treated animals, including the HSP-27 expressing foci (i.e. amygdala, piriform and entorhinal cortex, dentate gyrus). A general decrease of kainate receptor densities was observed together with an increase of NMDA binding sites in the hippocampus, the somatosensory, piriform and the entorhinal cortices. Furthermore, A1 binding sites were decreased in the amygdala and hippocampal CA1 region (CA1), while BZ binding sites were increased in the dentate gyrus and CA1. Our data demonstrate the impact of PTZ induced seizures on the densities of kainate, NMDA, A1 and BZ binding sites in epileptic brain. These changes are not restricted to regions showing glial impairment. Thus, an altered balance between different excitatory (NMDA) and modulatory receptors (A1, BZ binding sites, kainate) shows a much wider regional distribution than that of glial HSP-27 expression, indicating that receptor changes are not following the glial stress responses, but may precede the HSP-27 expression.

Section snippets

Animals

We used 8-week-old male Wistar rats (220–250 g body weight, Moellegaard Breeding Centre GmbH, Germany) for all experiments, and animals were housed under standard conditions as previously described (Rauca et al 2004, Bidmon et al 2005). All experimental procedures were conducted according to the institutional guidelines for the use of laboratory animals, the German Animal Welfare Act and approved by the responsible governmental agency.

PTZ treatment

Rats were injected intraperitoneally with PTZ (40 mg/kg body

Results

In PTZ-treated and control rats, mean densities (fmol/mg protein) of AMPA, kainate, NMDA, A1, GABAA, BZ and GABAB binding sites were measured in the amygdala, the piriform, entorhinal, somatosensory and retrosplenial granular cortices as well as in the hippocampal CA1 region (CA1) and the dentate gyrus (Fig. 1, Fig. 2, Table 2). Significant differences between control and PTZ-treated rats were found for kainate, NMDA, BZ and A1 binding sites (Fig. 3).

High densities of AMPA receptors were

Discussion

The aim of this study was to determine the effects of repeated PTZ-induced seizures on the densities of binding sites of different excitatory and inhibitory neurotransmitter receptors in the adult rat brain. A reduction of kainate receptor binding sites, but an increase of NMDA receptors as well as of BZ binding sites was found in most brain regions studied. The density of A1 receptor binding sites was reduced in a few regions.

PTZ was introduced as a GABAA antagonist (Macdonald and Barker, 1978

Acknowledgments

The authors appreciate the technical support by M. Cremer, S. Krause and S. Wilms. We would also like to thank A. Bauer for helpful comments on adenosine receptor properties.

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