Neurosteroids ameliorate conditioned fear stress: An association with sigma1 receptors

Yukihiro Noda, Hiroyuki Kamei, Yukie Kamei, Taku Nagai, Mikio Nishida, Toshitaka Nabeshima

研究成果: Article査読

51 被引用数 (Scopus)


Mice exhibited a marked suppression of motility (conditioned fear stress) when placed in an environment in which they had previously received an electric footshock. This conditioned fear stress response was dose-dependently attenuated by neurosteroids such as dehydroepiandrosterone sulfate (DHEAS; 25 and 50 mg/kg, s.c.) and pregnenolone sulfate (PREGS; 10-50 mg/kg, s.c.), and by a putative sigma1 receptor agonist, (+)-N-allylnormetazocine ((+)-SKF-10,047; 3 and 6 mg/kg, s.c.). However, progesterone (PROG; 10-50 mg/kg, s.c.) and allopregnanolone (5 and 20 mg/kg, s.c.) had no effect on this stress response. The attenuating effects of DHEAS (50 mg/kg, s.c.), PREGS (50 mg/kg, s.c.), and (+)-SKF-10,047 (6 mg/kg, s.c.) were reversed by NE-100 (5 mg/kg, i.p.), a sigma1 receptor antagonist and PROG (5 or 10 mg/kg, i.p.). When DHEAS (25 mg/kg) was co-administered with (+)-SKF-10,047 (3 mg/kg) at doses that do not affect the conditioned fear stress response by themselves, motor suppression was significantly attenuated. In mice showing the conditioned fear stress response, the serum concentration of DHEAS was lower than that in non-shocked mice. These results suggest that the attenuating effects of DHEAS and PREGS on the conditioned fear stress response are mediated via sigma1 receptors and that PROG has a sigma1 receptor antagonistic property. Further, the endogenous DHEAS may be involved in the expression of conditioned fear stress response in mice. Copyright (C) 2000 American College of Neuropsychopharmacology.

出版ステータスPublished - 01-09-2000

All Science Journal Classification (ASJC) codes

  • 薬理学
  • 精神医学および精神衛生


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