Antipsychotic drugs (APD's) therapy has been shown to be useful in the treatment of psychosis, however, after long term treatment some patients develop movement disorders. In order to be able to circumvent this problem much more must be known about how acute and chronic treatment with APD's affects dopaminergic areas of the brain. Herein we propose to use in vivo voltammetric and in vivo ion selective electrodes to study what effects acute and chronic administration of antipsychotic drugs have on dopamine release and potassium and calcium ion homeostasis in dopamine cell body and terminal regions. All of our proposed studies will be conducted in the rat. Specifically we plan to: (1) Determine the effects of acute and chronic administration of antipsychotic drugs on dopamine release in dopamine cell body (A9, A10 regions) and terminal regions (striatum, nucleus accumbens, prefrontal and cingulate cortices) in vivo using in vivo voltammetric techniques. (2) Determine what effects acetylcholine, gamma aminobutyric acid (GABA), cholecystokinin, neurotensin, and glutamic acid have on dopamine release in dopamine cell body and terminal regions in vivo using in vivo voltammetric techniques. (3) Determine what effects acute and chronic administration of antipsychotic drugs have on the dopaminergic release influences exerted by the substances in (2) above. (4) Determine what effects acute and chronic administration of antipsychotic drugs have on the homeostasis of potassium and calcium ions in vivo using in vivo ion selective electroanalytical techniques. (5) Determine the stoichiometries and equilibrium constants of the newly observed direct chemical interaction between antipsychotic drugs and dopamine and neurotensin and dopamine. The potential functional significance of these interactions will be assessed in in vitro and in vivo studies, and (6) Develop methods for direct monitoring of antipsychotic drugs in vivo.
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