Activation of both dopamine D1 and D2 receptors necessary for amelioration of conditioned fear stress.
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 D1 receptor agonist, SKF 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1-H-3-benzazepine), and the dopamine D2 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 D1 receptor antagonist, SCH 23390 (R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H- 3-benzazepine), and by the dopamine D2 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 D1 and D2 receptors is necessary to attenuate this stress-induced motor suppression.
Kamei
H
H
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Kameyama
T
T
Nabeshima
T
T
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004597:Electroshock; D004873:Ergolines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005239:Fear / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D019257:Quinpirole; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D012055:Reinforcement Schedule; D013315:Stress, Psychological / Q000188:drug therapy* / Q000523:psychology; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D004873:Ergolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D001058:Apomorphine