Title

Neurochemical interactions in an animal model of parkinsonian tremor: Behavior, pharmacology, and the role of transcription factors as markers of striatal cell activity

Date of Completion

January 2006

Keywords

Biology, Neuroscience|Psychology, Psychobiology|Psychology, Behavioral

Degree

Ph.D.

Abstract

A series of 21 experiments were performed to study the effects of typical and atypical antipsychotics in terms of their ability to induce tremulous jaw movements (TJMs), to characterize the pharmacological interactions that regulate TJMs, and to identify cell signaling molecules that could be used as markers of the neural processes related to the generation of TJMs. The studies in Chapter 2 investigated the behavioral effects of the typical antipsychotic pimozide. Chapter 3 investigated immediate early gene (IEG) expression after sub-chronic administration of pimozide and its relation to behavior. The experiments in Chapter 4 investigated the behavioral effects of the atypical antipsychotic quetiapine, while Chapter 5 focused on IEG expression after sub-chronic administration of quetiapine and its relation to behavior. Chapter 6 consisted of behavioral pharmacology studies that focused upon the ability of drugs from various classes (i.e., 5HT2A/C antagonists, dopamine D1 receptor antagonists, muscarinic antagonists and adenosine A2A antagonists) to attenuate drug-induced TJM activity in order to characterize the effects of drugs that have putative antiparkinsonian characteristics. The last group of experiments (Chapter 7) investigated the reversal of dopamine antagonist-induced IEG expression in the striatum with adenosine A2A and acetylcholinergic muscarinic M4 antagonism. Taken together, the present studies have provided further evidence for the action of pimozide exerting its "typical" antipsychotic effects via blockade of DA receptors in the basal ganglia and that the TJM model can be useful for assessing the effects of antiparkinsonian drugs from a variety of different classes after sub-chronic administration of pimozide. In summary, the research presented may help to characterize the specific role that striatal activity plays in the neuronal networks of the basal ganglia, and how intracellular responses ultimately can be related to specific aspects of motor function. ^