Immunocytochemical analysis of glutamate and GABA in selectively bred mice.
Withdrawal Seizure Prone (WSP) and Withdrawal Seizure Resistant (WSR) mice have been selectively bred for differential ethanol withdrawal handling-induced convulsions (HICs). In addition, it has been observed that WSP mice exhibit drug-naive HICs. This latter finding suggests that WSP and WSR mice differ in their susceptibility to HICs. Alterations in the glutamate and gamma-aminobutyric acid (GABA) systems have been implicated in convulsive activity and have been proposed to underlie the manifestation of ethanol withdrawal symptoms. It is therefore possible that WSP and WSR mice are genetically different with respect to their glutamatergic and/or GABAergic systems. To test this hypothesis, we have analyzed WSP and WSR mice that are both drug- and HIC-naive for differences in the density of nerve terminal glutamate and GABA immunoreactivity within the CA1 subfield of the hippocampus (CA1) and layer II of the somatosensory cortex (SSC). The major finding of this study is that drug- and HIC-naive WSP mice exhibit a significantly greater density of presynaptic glutamate immunoreactivity associated with asymmetric synapses within the CA1, but not the SSC, when compared to WSR mice. The density of GABA immunoreactivity within nerve terminals associated with symmetric synapses does not differ between the selected lines in either brain region. Since prior drug exposure and HICs cannot account for the observed differences in these naive mice, the results strongly suggest that the density of nerve terminal glutamate immunoreactivity within the CA1 is a reflection of inherent genetic differences between WSP and WSR mice. Furthermore, an elevated density of presynaptic glutamate immunoreactivity may be an underlying neurochemical correlate to increased susceptibility to drug-naive and ethanol withdrawal convulsions.
Buckman
J F
JF
Department of Behavioral Neuroscience, Oregon Health Sciences University, Portland 97201, USA.
Meshul
C K
CK
D000818:Animals; D005260:Female; D018698:Glutamic Acid / Q000276:immunology* / Q000378:metabolism; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D005680:gamma-Aminobutyric Acid / Q000276:immunology* / Q000378:metabolism
D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid