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Analgesic effects of the neurosteroid 3 alpha-androstanediol.

Abstract：

:The efficacy of 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-Androstanediol; 3 alpha-Diol) and 4-pregnen-3,20-dione (progesterone; P) in promoting analgesia was investigated. Ovariectomized rats received daily injections of 3 alpha-Diol (0.6, 3.0, 6.0 and 7.5 mg/kg) or vehicle and twice daily injections of estradiol-17 beta (E2: 1 microgram) for 2 days. Progesterone (0.5, 1.0, 2.0 and 4.0 mg/kg) or its vehicle was given on the third day and nociceptive testing using the radiant heat tailflick method was carried out 4 h later. In Expt. 1, P and 3 alpha-Diol both produced analgesia and had biphasic dose-response effects when administered singly. 3 alpha-Diol (3.0 mg/kg) elevated tailflick latencies in E2-primed animals above those following vehicle, 6.0 or 7.5 mg/kg 3 alpha-Diol; 6.0 and 7.5 mg/kg produced elevations that were greater than vehicle but less than 3.0 mg/kg. Progesterone (0.5 and 1.0 mg/kg) also elevated tailflick latencies above vehicle controls, while 2.0 and 4.0 mg/kg produced intermediate effects. In Expt. 2, 3 alpha-Diol (3 alpha-Diol:BSA) and P (P:BSA) conjugated to bovine serum albumin (BSA) were applied to the medial basal hypothalamus (MBH) and preoptic area (POA) to ascertain whether the steroids' analgesic actions were mediated by membrane actions in these sites. Free P and P:BSA both increased tailflick latencies when applied to the MBH, while 3 alpha-Diol and 3 alpha-Diol:BSA elevated latencies when applied to the POA, suggesting the steroids' effects occur in part at the neuronal membrane. In Expt. 3, free P or P:BSA applied to the MBH did not increase tailflick latencies if systemic P was given concurrently. Similarly, free 3 alpha-Diol and 3 alpha-Diol:BSA implants into the POA failed to increase tailflick latencies if s.c. 3 alpha-Diol was co-administered. These data indicate that P and 3 alpha-Diol at moderate doses have analgesic effects in part via membrane actions within the MBH and POA, respectively.

journal_name

Brain Res

journal_title

Brain research

authors

Frye CA,Van Keuren KR,Rao PN,Erskine MS

doi

10.1016/0006-8993(95)01118-8

subject

Has Abstract

pub_date

1996-02-12 00:00:00

pages

1-9

issue

eissn

0006-8993

issn

1872-6240

pii

0006899395011188

journal_volume

709

pub_type

杂志文章

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Analgesic effects of the neurosteroid 3 alpha-androstanediol.