TY - JOUR
T1 - SKF-10,047 reverses stress-induced motor suppression
T2 - interaction with dopaminergic system
AU - Kamei, Hiroyuki
AU - Kameyama, Tsutomu
AU - Nabeshima, Toshitaka
N1 - Funding Information:
We thank Dr. A.K. Cho, Fujisawa Pharmaceutical Co. and Bristol Myers Squibb for supplying ( + )-N-allylnormetazocine hydrochloride, pimozide and BMY-14802, respectively. This study was supported, in part, by a Grant-in-Aid for Science Research (No. 03304036 and 00092093) from the Ministry of Education, Science and Culture, Japan and a grant from the Ministry of Health and Welfare Foundation for Drug Abuse (No. 92-268).
PY - 1994/7/21
Y1 - 1994/7/21
N2 - 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 σ receptor agonist, but not by its (-)-optical isomer ((-)-SKF-10,047) and the σ receptor ligands (+)-pentazocine and 1,3-di(2-tolyl)guanidine. This effect of (±)-SKf-10,047 was antagonized by BMY-14802, a σ 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 σ receptors, which are closely linked to the dopaminergic neuronal system.
AB - 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 σ receptor agonist, but not by its (-)-optical isomer ((-)-SKF-10,047) and the σ receptor ligands (+)-pentazocine and 1,3-di(2-tolyl)guanidine. This effect of (±)-SKf-10,047 was antagonized by BMY-14802, a σ 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 σ receptors, which are closely linked to the dopaminergic neuronal system.
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U2 - 10.1016/0014-2999(94)90007-8
DO - 10.1016/0014-2999(94)90007-8
M3 - Article
C2 - 7957624
AN - SCOPUS:0028363286
SN - 0014-2999
VL - 260
SP - 39
EP - 46
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -