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

• Published in: Psychopharmacologia 1985-01, Vol.87 (3), p.308-312
• Main Authors: PUGH, M. T, O'BOYLE, K. M, MOLLOY, A. G, WADDINGTON, J. L
• Format: Article
• Language: English
• Subjects: Animals; Benzazepines - pharmacology; Binding, Competitive; Biological and medical sciences; Catecholaminergic system; Corpus Striatum - metabolism; Drug Interactions; In Vitro Techniques; Isoquinolines - pharmacology; Male; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Phenethylamines - pharmacology; Rats; Rats, Inbred Strains; Receptors, Dopamine - drug effects; Receptors, Dopamine - metabolism; Receptors, Dopamine D1; Receptors, Dopamine D2; Stereotyped Behavior - drug effects
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/BF00432713

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 stereo-typed behaviour characterised by continuous downward sniffing and locomotion. These responses were antagonised, as expected, by 40-200 micrograms/kg Ro22-2586, but surprisingly blocked by 40-200 micrograms/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 3H-piflutixol to striatal D-1 receptors and of 3H-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 micrograms/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 by D-2 dopaminergic stimulation.