Modification of the behavioral effects of the selective dopamine D2 agonist (+)-4-propyl-9-hydroxynaphthoxazine by dopamine antagonists in monkeys

S Rosenzweig-Lipson and J Bergman

Harvard University, Department of Psychology, Cambridge, Massachusetts.

The present studies were conducted to evaluate the modification of the behavioral effects of the selective D2 agonist (+)-4-propyl-9- hydroxynaphthoxazine [(+)-PHNO] by dopamine receptor blockade. In squirrel monkeys responding under a fixed-ratio schedule of stimulus- shock termination, the effects of (+)-PHNO were determined alone and in combination with the selective D2 antagonist eticlopride, the selective D1 antagonist (-)-trans-6,7,7a,8,9,13b- hexahydro-3-chloro-2-hydroxy-N- methyl-5H-benzo(d)naphtho-(2,1)azepine (SCH 39166), the nonselective D1/D2 antagonist cis-flupentixol or the atypical neuroleptic clozapine. When administered alone, (+)-PHNO produced dose-dependent decreases in rates of responding. Pretreatment with eticlopride and cis-flupentixol resulted in dose-dependent right-ward shifts of the (+)-PHNO dose- effect curve, indicative of surmountable antagonism. Pretreatment with SCH 39166 and clozapine failed to antagonize the effects of (+)-PHNO and resulted in a downward shift of the (+)-PHNO dose-effect curve. Other experiments were conducted to determine the duration of either catalepsy-associated behavior or repetitive scratching produced by (+)- PHNO alone and in combination with selected dopamine receptor blockers. Low doses of (+)-PHNO (0.001-0.003 mg/kg) increased the duration of catalepsy-associated behavior, whereas higher doses (0.003-0.01 mg/kg) restored the duration of catalepsy-associated behavior to control values and produced increases in the duration of repetitive scratching.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 265, Issue 3, pp. 1039-1046, 06/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics

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