Author

Stratman

Date of Award

6-1995

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Dr. Robert Lahti

Second Advisor

Dr. William Jackson

Third Advisor

Dr. Montford Piercey

Fourth Advisor

Dr. Leonard Beuving

Access Setting

Masters Thesis-Open Access

Abstract

Extrapyramidal side effects (EPS) are associated with most antipsychotics for the treatment of schizophrenia since these agents antagonize dopamine D2 receptors in the nigrostriatal pathway, a brain system that regulates motor functions. Clozapine, an atypical antipsychotic agent in that it does not produce EPS, was found to be more selective for the D4 than the D2 receptor. The purpose of this study was to locate the D4 receptor in rat brain by autoradiographic comparison studies with [3H]YM-09151-2, a D2 , D3, and D4 radioligand, to [3H]raclopride, a D2 and D3 radioligand, in which a subtraction would identify D4 receptor distribution. Blocking studies were also performed by inhibiting [3H]YM-09151-2 with raclopride and clozapine.

Receptor binding density of [3H]YM-09151-2 was greater than [3H]raclopride in mesocorticolimbic regions, a brain system involved in cognition and emotional stability, and clozapine blocked [3H]YM-09151-2 in these regions. Raclopride inhibited [3H]YM-09151-2 in nigrostriatal regions, whereas clozapine had no effect. The investigation demonstrates that D4 receptor antagonism may result in antipsychotic efficacy without EPS.

Included in

Biology Commons

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