Receptor-Binding Studies of Agonists and Antagonists at the D2 Dopamine Receptor in Bovine Caudate

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Authors
Francis, Jonathan W.
Issue Date
1984
Type
Thesis
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en_US
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Abstract
Antipsychotic drugs are thought to produce their therapeutic effects in schizophrenia by blocking receptors for the neurotransmitter dopamine in the brain. Several lines of evidence previously indicated, however, that 3H-spiperone labels a heterogeneous population of receptors in radioligand binding studies. In the present study, the ability of various dopaminergic agonists (apomorphine, bromoergocryptine, and dopamine) and antagonists (chlorpromazine and clozapine) to inhibit 3H-spiperone binding was determined under conditions where certain subpopulations of receptors labeled by this radioligand were blocked by various masking agents. The masking agents used were dopamine, clozapine, and the selective serotonergic antagonist, ketanserin. In the studies where dopamine was used as a masking agent, there was a statistically significant increase in the inhibitory potency of clozapine. Conversely, when clozapine was used as a masking agent, the inhibitory potency of dopamine was enhanced. Whereas ketanserin significantly increased the inhibitory potency of dopamine, it also significantly decreased the inhibitory potency of clozapine. The results generated by these investigations suggest that 3H-spiperone labels at least 3 different binding sites in bovine caudate. One group of sites appears to be serotonergic, while the remaining sites may be two distinct subpopulations of dopamine receptor which differ in their affinity for dopamine.
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v, 31 p.
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Kalamazoo College
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U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.
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