SKF-10,047 reverses stress-induced motor suppression: interaction with dopaminergic system.
Mice exhibited a marked suppression of motility (conditioned suppression) when placed in the same environment in which they had previously received an electric footshock. This stress-induced motor suppression was dose dependently attenuated by (+/-)-SKF-10,047, a sigma receptor agonist, but not by its (-)-optical isomer ((-)-SKF-10,047) and the sigma receptor ligands (+)-pentazocine and 1,3-di-(2-tolyl)guanidine. This effect of (+/-)-SKF-10,047 was antagonized by BMY-14802, a sigma receptor antagonist, and by pimozide, a dopamine receptor antagonist. When dopaminergic neurons were destroyed by pretreatment with 6-hydroxydopamine, the effect of (+/-)-SKF-10,047 on the stress response was also attenuated. Furthermore, (+/-)-SKF-10,047 dose dependently reversed the decrease in striatal dopamine turnover in the conditioned suppression group. These results suggest that stress-induced motor suppression is restored by (+/-)-SKF-10,047 acting through sigma receptors, which are closely linked to the dopaminergic neuronal system.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
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Kamei
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Kameyama
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Nabeshima
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000927:Anticonvulsants / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004597:Electroshock; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D016627:Oxidopamine / Q000494:pharmacology; D010423:Pentazocine / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D017480:Receptors, sigma / Q000187:drug effects / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy* / Q000523:psychology
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D006146:Guanidines; D011743:Pyrimidines; D017480:Receptors, sigma; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; D010868:Pimozide; D008694:Methamphetamine; C012134:SK&F 10047; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D016627:Oxidopamine; D010620:Phenazocine; C050232:1,3-ditolylguanidine; D001058:Apomorphine; D010423:Pentazocine; D004298:Dopamine