Effects of the putative D-1 antagonist SCH 23390 on stereotyped behaviour induced by the D-2 agonist RU24213

Effects of the putative D-1 antagonist SCH 23390 on stereotyped behaviour induced by the D-2... 213 87 87 3 3 Mark T. Pugh Kathy M. O'Boyle Anthony G. Molloy John L. Waddington Department of Clinical Pharmacology Royal College of Surgeons in Ireland St. Stephen's Green Dublin 2 Ireland Abstract The effects of the putative selective dopamine D-1 antagonist benzazepine SCH 23390 and of the selective dopamine D-2 antagonist Ro22-2586 on stereotypy induced by the selective D-2 agonist RU24213 were compared. RU24213 (0.5–15 mg/kg) dose-dependently induced stereotyped behaviour characterised by continuous downward sniffing and locomotion. These responses were antagonised, as expected, by 40–200 μg/kg Ro22-2586, but surprisingly blocked by 40–200 μg/kg SCH 23390. The selectivities of these compounds for dopamine receptor subtypes were verified in terms of their relative abilities to displace the in vitro binding of 3 H-piflutixol to striatal D-1 receptors and of 3 H-spiperone to D-2 receptors. As SCH 23390 fails to influence D-2 mediated prolactin secretion or emesis in vivo, there appears to be no significant formation of an active metabolite of SCH 23390 with D-2 antagonist activity. Because SCH 23390 has some affinity for 5-hydroxytryptamine receptors, any effect on the serotonergic behavioural syndrome induced by 10 mg/kg 5-methoxy-N,N-dimethyltryptamine was also studied. The serotonergic responses of hind limb abduction, reciprocal forepaw treading and Straub tail were unaltered after 40–200 μg/kg SCH 23390, indicating no significant 5-HT blockade or non-specific depressant action at these doses which might influence the expression of stereotypy. Thus, these data are consistent with blockade of tonic D-1 dopaminergic activity that may influence the expression of behaviours initiated byD-2 dopaminergic stimulation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Psychopharmacology Springer Journals

Effects of the putative D-1 antagonist SCH 23390 on stereotyped behaviour induced by the D-2 agonist RU24213

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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/BF00432713
Publisher site
See Article on Publisher Site

Abstract

213 87 87 3 3 Mark T. Pugh Kathy M. O'Boyle Anthony G. Molloy John L. Waddington Department of Clinical Pharmacology Royal College of Surgeons in Ireland St. Stephen's Green Dublin 2 Ireland Abstract The effects of the putative selective dopamine D-1 antagonist benzazepine SCH 23390 and of the selective dopamine D-2 antagonist Ro22-2586 on stereotypy induced by the selective D-2 agonist RU24213 were compared. RU24213 (0.5–15 mg/kg) dose-dependently induced stereotyped behaviour characterised by continuous downward sniffing and locomotion. These responses were antagonised, as expected, by 40–200 μg/kg Ro22-2586, but surprisingly blocked by 40–200 μg/kg SCH 23390. The selectivities of these compounds for dopamine receptor subtypes were verified in terms of their relative abilities to displace the in vitro binding of 3 H-piflutixol to striatal D-1 receptors and of 3 H-spiperone to D-2 receptors. As SCH 23390 fails to influence D-2 mediated prolactin secretion or emesis in vivo, there appears to be no significant formation of an active metabolite of SCH 23390 with D-2 antagonist activity. Because SCH 23390 has some affinity for 5-hydroxytryptamine receptors, any effect on the serotonergic behavioural syndrome induced by 10 mg/kg 5-methoxy-N,N-dimethyltryptamine was also studied. The serotonergic responses of hind limb abduction, reciprocal forepaw treading and Straub tail were unaltered after 40–200 μg/kg SCH 23390, indicating no significant 5-HT blockade or non-specific depressant action at these doses which might influence the expression of stereotypy. Thus, these data are consistent with blockade of tonic D-1 dopaminergic activity that may influence the expression of behaviours initiated byD-2 dopaminergic stimulation.

Journal

PsychopharmacologySpringer Journals

Published: Nov 1, 1985

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