IMMUNOCYTOCHEMICAL ANALYSIS OF GLUTAMATE AND GABA IN SELECTIVELY BREDMICE

Withdrawal Seizure Prone (WSP) and Withdrawal Seizure Resistant (WSR) mice have been selectively bred for differential ethanol withdrawal ha ndling-induced convulsions (HICs). In addition, it has been observed t hat WSP mice exhibit drug-naive HICs. This latter finding suggests tha t 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 poss ible that WSP and WSR mice are genetically different with respect to t heir glutamatergic and/or GABAergic systems. To test this hypothesis, we have analyzed WSP and WSR mice that are both drug- and HIC-naive fo r differences in the density of nerve terminal glutamate and GABA immu noreactivity within the CA1 subfield of the hippocampus (CA1) and laye r II of the somatosensory cortex (SSC). The major finding of this stud y is that drug- and HIC-naive WSP mice exhibit a significantly greater density of presynaptic glutamate immunoreactivity associated with asy mmetric synapses within the CA1, but not the SSC, when compared to WSR mice. The density of GABA immunoreactivity within nerve terminals ass ociated with symmetric synapses does not differ between the selected l ines 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 immunor eactivity within the CA1 is a reflection of inherent genetic differenc es between WSP and WSR mice. Furthermore, an elevated density of presy naptic glutamate immunoreactivity may be an underlying neurochemical c orrelate to increased susceptibility to drug-naive and ethanol withdra wal convulsions.