In vivo microdialysis study of the release and metabolism of dopamine,serotonine,and amino acid neurotransmitters in rat basal ganglia and hippocampus

This project concerns the application of single and dual probe techniques, coupled to microbore HPLC, for the pharmacological study of the release and metabolism of monoamine and amino acid neurotransmitters in rat CNS. The role of 5-HT receptor subtypes will be evaluated using local application of selective 5-HT recepotor agonists and antagonists in the hippocampus and the raphe nuclei: new generation antipsychotics (eg. risperidone), antidepressants and antiepileptics. The second part of this work deals with the further study of dopamine outflow and biotransformation of levodopa into dopamine at the level of the striatum and substantia nigra (S.N.). Thereby we use the "hemi-parkinson" model, (lesioning of the nigrostriatal pathway by 6-OH-dopamine) and evaluate the effect of dopaminergic agonists and antagonists. In the same animal model the effect of intranigral cholinergic Ml and M2 cholinergic agents on dopamine release in striatum and S.N. can be evaluated. Finally, we also focus our attention to the GABA-ergic and glutamatergic neurotransmission in the corticostriatal and striatonigral pathways. Thereby we use kainic acid lesions of the striatum as well as different types of cortical lesions in combination with cholinergic, dopaminergic and GABA-ergic manipulations.