The Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) mice were selectively bred, in replicate, to display differential susceptibility to handling-induced convulsions (HICs) during ethanol withdrawal. By characterizing neurochemical differences that exist between these lines, it may be possible to elucidate gene products associated with increased risk for becoming drug dependent (measured by severity of withdrawal). The goal of this project is to characterize glutamate uptake in WSP and WSR mice to determine whether these types of alterations in glutamate functioning are involved in conferring susceptibility and resistance to HICs. Affinity and maximal L-[3H] glutamate uptake in hippocampal and frontal cortical synaptosomes will be analyzed with biochemical uptake assays. Neuronal uptake in synaptosomes will also be assessed using electron microscopy combined with an immuno-gold immuno-cytochemical technique. The subjects will include both replicate lines of WSP and WSR mice that are: (1) ethanol- and convulsion-naive; (2) ethanol-naive, but convulsed; (3) convulsion- naive, but withdrawn after acute ethanol; (4) convulsed and withdrawn after acute ethanol; (5) convulsion-naive, but withdrawn after chronic ethanol. Alcoholism is a prominent social problem that is, at least, partially inherited. The experiments proposed in this fellowship will analyze genetic and neurochemical factors associated with differential susceptibility to drug abuse.
| Buckman, J F; Meshul, C K (1999) Glial differences between naive withdrawal seizure-prone and -resistant mice. Alcohol Clin Exp Res 23:1905-13 |
| Meshul, C K; Emre, N; Nakamura, C M et al. (1999) Time-dependent changes in striatal glutamate synapses following a 6-hydroxydopamine lesion. Neuroscience 88:1-16 |
