Neurosteroids ameliorate conditioned fear stress: An association with sigma1 receptors

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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)276-284
Number of pages9
JournalNeuropsychopharmacology
Volume23
Issue number3
DOIs
Publication statusPublished - 01-09-2000
Externally publishedYes

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Fear
Neurotransmitter Agents
Pregnanolone
Dehydroepiandrosterone Sulfate
Progesterone
Serum

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Noda, Yukihiro ; Kamei, Hiroyuki ; Kamei, Yukie ; Nagai, Taku ; Nishida, Mikio ; Nabeshima, Toshitaka. / Neurosteroids ameliorate conditioned fear stress : An association with sigma1 receptors. In: Neuropsychopharmacology. 2000 ; Vol. 23, No. 3. pp. 276-284.
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Neurosteroids ameliorate conditioned fear stress : An association with sigma1 receptors. / Noda, Yukihiro; Kamei, Hiroyuki; Kamei, Yukie; Nagai, Taku; Nishida, Mikio; Nabeshima, Toshitaka.

In: Neuropsychopharmacology, Vol. 23, No. 3, 01.09.2000, p. 276-284.

Research output: Contribution to journalArticle

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