Opposite modulation of apomorphine- or amphetamine-induced stereotypy by antagonists of CCK receptors

Abstract

Stereotyped behavior is elicited by activation of dopaminergic systems with drugs such as apomorphine and amphetamine. In previous studies, we have reported that the sulfated cholecystokinin octapeptide (CCK-8) decreased apomorphine-induced stereotypy in animals with normal and supersensitive dopamine receptors. The aim of the present study was to evaluate the effects of CCK 1 and CCK 2 receptor antagonists on stereotyped behavior induced by apomorphine or amphetamine. Rats were pretreated with the CCK 1 (SR 27897B; 1-[[2-(4-(2-chlorophenyl) thiazol-2-yl) aminocarbonyl]indolyl]acetic acid; 500 μg/kg; i.p.) or CCK 2 (L-365,260; 3R-(+)- N-(2,3-dihydro-1-methyl-2-oxo-5 phenyl-1 H-1,4-benzodiazepine-3-yl)- N′-(3-methyl phenyl)-urea; 500 μg/kg; i.p.) receptor antagonists or saline 15 min before apomorphine (0.6 mg/kg; s.c.) or amphetamine (9.0 mg/kg; i.p.) injection. Both CCK 1 and CCK 2 receptor antagonists significantly increased apomorphine-induced stereotypy. In contrast, only the blockade of CCK 2 receptors significantly decreased amphetamine-induced stereotypy. The results suggest a dual opposite mechanism for CCK–dopamine interactions. These data also suggest that both apomorphine- and amphetamine-induced stereotypy should be used whenever effects of drugs acting on dopaminergic systems are being assessed.