The use of in vivo binding methods to study the pharmacology of receptors in the rat central nervous system.
Item
-
Title
-
The use of in vivo binding methods to study the pharmacology of receptors in the rat central nervous system.
-
Identifier
-
AAI9618063
-
identifier
-
9618063
-
Creator
-
Duffy, Ruth Anne.
-
Contributor
-
Adviser: Victoria Luine
-
Date
-
1996
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Biology, Neuroscience | Psychology, Physiological
-
Abstract
-
These studies examine the use of in vivo receptor binding methodologies to determine the pharmacology of antagonists at receptors in the central nervous system. The utility of in vivo binding methods as a tool to measure receptor occupancy within an intact biological system was demonstrated. Specifically, these studies describe the use of in vivo binding methods to determine the penetrability of radiolabeled ligands specific for dopaminergic and muscarinic receptors into the CNS, as well as their dose-dependent inhibition by selective antagonists. The unique contribution of these studies is that by determining the percentage of receptors occupied by various antagonists, a correlation between receptor occupancy and specific behavioral effects can be made.;In the dopaminergic studies, {dollar}\sp3{dollar}H-SCH 39166, a D1 selective antagonist, was administered to rats s.c. with competing antagonists, including D1, D2 and non-selective dopamine antagonists. The EC{dollar}\sb{lcub}50{rcub}{dollar} values were obtained and compared with their EC{dollar}\sb{lcub}50{rcub}{dollar} values against the D2 antagonist {dollar}\sp3{dollar}H-raclopride. It was found that D1 antagonists displaced {dollar}\sp3{dollar}H-SCH 39166 with the highest affinity, D2 antagonists displaced {dollar}\sp3{dollar}H-raclopride with the greatest affinity, and that the mixed antagonists had activity at both receptors. Significant correlations between both D1 and D2 antagonist affinity and minimal effective doses for the conditioned avoidance response (CAR) test suggest that this behavioral effect is mediated through dopamine receptors. In addition, ex vivo studies were performed to confirm the results found using in vivo methodologies.;Similar in vivo studies were performed using {dollar}\sp3{dollar}H-scopolamine to examine muscarinic cholinergic receptors in the CNS and periphery. Results indicate that antagonists which cross the blood-brain barrier had the highest affinity, while those that do not cross had low affinity. Regional differences in binding were seen, which were further studied by examining differences in kinetics and the affinity of {dollar}\sp3{dollar}H-scopolamine for the different muscarinic receptor subtypes m1-m5. A significant correlation between EC{dollar}\sb{lcub}50{rcub}{dollar} values for in vivo binding and MED values for passive avoidance responding, a behavioral test associated with learning and memory, and muscarinic receptors, was found.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
