Activation of both dopamine D 1 and D 2 receptors necessary for amelioration of conditioned fear stress

Abstract

Mice exhibited a marked suppression of motility when they were re-placed in the same environment in which they had previously received an electric footshock. This psychological stress-induced motor suppression, known as conditioned fear stress, was dose dependently attenuated by apomorphine, a non-selective dopamine receptor agonist. Combined treatment with the dopamine D 1 receptor agonist, SKF 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1-H-3-benzazepine), and the dopamine D 2 receptor agonist, quinpirole, also synergistically attenuated the conditioned fear stress although, alone, neither SKF 38393 nor quinpirole did so at the doses used. The effects of apomorphine and of the coadministration of SKF 38393 and quinpirole on the conditioned fear stress were completely blocked by the dopamine D 1 receptor antagonist, SCH 23390 ( R-(+)-7-chloro-8-hy-droxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine), and by the dopamine D 2 receptor antagonist, (−)-sulpiride. These results suggest that a dysfunction in the dopaminergic neuronal system is responsible for the conditioned fear stress, and that the activation of both dopamine D 1 and D 2 receptors is necessary to attenuate this stress-induced motor suppression.