Differential involvement of dopamine D-1 and D-2 receptors in the circling behaviour induced by apomorphine, SK & F 38393, pergolide and LY 171555 in 6-hydroxydopamine-lesioned rats

Differential involvement of dopamine D-1 and D-2 receptors in the circling behaviour induced by... 213 85 85 3 3 Jørn Arnt John Hyttel Department of Pharmacology and toxicology H. Lundbeck A/S Ottiliavej 7-9 DK-2500 Copenhagen-Valby Denmark Abstract The antagonistic effect of dopamine (DA) D-1 and D-2 antagonists against circling behaviour induced by various DA agonists in 6-OHDA-lesioned rats has been investigated. DA D-1/D-2 selectivity of agonists in vitro was measured by the stimulatory effect on DA-sensitive adenylate cyclase in rat striatal homogenates (D-1), the inhibitory effect on electrically-induced release of 3 H-DA in rabbit striatal slices (D-2) and the affinity to 3 H-piflutixol (D-1) and 3 H-spiroperidol (D-2) binding sites in rat striatal membranes. The contralateral circling behaviour induced by the DA D-1 agonist SK & F 38393 was blocked by the DA D-1 antagonist, SCH 23390, and by the mixed DA D-1/D-2 antagonist cis (Z)-flupentixol, but was not influenced by the DA D-2 antagonists spiroperidol and clebopride. In contrast, circling behaviour induced by the preferential DA D-2 agonists pergolide and LY 171555 was blocked by clebopride, spiroperidol, and cis (Z)-flupentixol, but weakly or not influenced by SCH 23390. Apomorphine-induced circling behaviour was blocked by cis (Z)-flupentixol, partially antagonized by SCH 23390 and clebopride but not inhibited by spiroperidol, although the time-course of circling was changed. Combinations of SCH 23390 with spiroperidol or clebopride in low doses completely blocked the effect of apomorphine. These results indicate that DA D-1 and D-2 receptors mediate circling behaviour through separate mechanisms which can be independently manipulated with respective agonists and antagonists. Furthermore, the results indicate that both DA D-1 and D-2 receptors are involved in the effect of apomorphine, since selective antagonists induced maximally 50% inhibition. Complete blockade was only found in combination experiments and by the mixed D-1/D-2 antagonists cis (Z)-flupentixol, cis (Z)-clopenthixol, and clozapine. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Psychopharmacology Springer Journals

Differential involvement of dopamine D-1 and D-2 receptors in the circling behaviour induced by apomorphine, SK & F 38393, pergolide and LY 171555 in 6-hydroxydopamine-lesioned rats

Psychopharmacology, Volume 85 (3) – Mar 1, 1985

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Publisher
Springer Journals
Copyright
Copyright © 1985 by Springer-Verlag
Subject
Biomedicine; Pharmacology/Toxicology; Psychiatry
ISSN
0033-3158
eISSN
1432-2072
D.O.I.
10.1007/BF00428200
Publisher site
See Article on Publisher Site

Abstract

213 85 85 3 3 Jørn Arnt John Hyttel Department of Pharmacology and toxicology H. Lundbeck A/S Ottiliavej 7-9 DK-2500 Copenhagen-Valby Denmark Abstract The antagonistic effect of dopamine (DA) D-1 and D-2 antagonists against circling behaviour induced by various DA agonists in 6-OHDA-lesioned rats has been investigated. DA D-1/D-2 selectivity of agonists in vitro was measured by the stimulatory effect on DA-sensitive adenylate cyclase in rat striatal homogenates (D-1), the inhibitory effect on electrically-induced release of 3 H-DA in rabbit striatal slices (D-2) and the affinity to 3 H-piflutixol (D-1) and 3 H-spiroperidol (D-2) binding sites in rat striatal membranes. The contralateral circling behaviour induced by the DA D-1 agonist SK & F 38393 was blocked by the DA D-1 antagonist, SCH 23390, and by the mixed DA D-1/D-2 antagonist cis (Z)-flupentixol, but was not influenced by the DA D-2 antagonists spiroperidol and clebopride. In contrast, circling behaviour induced by the preferential DA D-2 agonists pergolide and LY 171555 was blocked by clebopride, spiroperidol, and cis (Z)-flupentixol, but weakly or not influenced by SCH 23390. Apomorphine-induced circling behaviour was blocked by cis (Z)-flupentixol, partially antagonized by SCH 23390 and clebopride but not inhibited by spiroperidol, although the time-course of circling was changed. Combinations of SCH 23390 with spiroperidol or clebopride in low doses completely blocked the effect of apomorphine. These results indicate that DA D-1 and D-2 receptors mediate circling behaviour through separate mechanisms which can be independently manipulated with respective agonists and antagonists. Furthermore, the results indicate that both DA D-1 and D-2 receptors are involved in the effect of apomorphine, since selective antagonists induced maximally 50% inhibition. Complete blockade was only found in combination experiments and by the mixed D-1/D-2 antagonists cis (Z)-flupentixol, cis (Z)-clopenthixol, and clozapine.

Journal

PsychopharmacologySpringer Journals

Published: Mar 1, 1985

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