Effect of thyrotropin releasing hormone on U-50,488H-induced pharmacological responses in mice.

Abstract:

:The effect of thyrotropin releasing hormone (TRH) administered either subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) on the analgesic and hypothermic actions of U-50,488H, a highly selective kappa-opiate agonist, was determined in male Swiss Webster mice. Intraperitoneal administration of U-50,488H (8-32 mg/kg) produced a dose-dependent analgesia as assessed by the tail-flick test. Similarly, U-50,488H also produced a dose-dependent hypothermia in mice. TRH was administered s.c. 15 min or i.c.v. 5 min prior to U-50,488H injection. TRH (1,3 and 10 mg/kg, s.c.) dose-dependently attenuated the analgesic effect of U-50,488H (32 mg/kg), whereas TRH at these doses displayed almost complete blockade of the hypothermic effect of U-50,488H. Similarly, TRH (0.03, 0.3 and 1 microgram/mouse; i.c.v.) dose-dependently attenuated the analgesic and hypothermic actions of U-50,488H, indicating the central component in the action of TRH. TRH alone in doses used showed no change in either basal tail-flick latency or body temperature, demonstrating the lack of effect of this drug alone on pain and temperature responsiveness. Studies have shown that TRH does not modify morphine or beta-endorphin-induced analgesia in animals nor does it affect the binding of mu-opiate agonist or antagonist to brain membranes. Previous studies from this laboratory have indicated that kappa-opiates but not mu-opiates inhibit the binding of [3H][3-MeHis2]-TRH to brain membranes. The present studies clearly show that TRH modulates the pharmacological actions mediated by kappa-opiate agonists in mice. Thus, these studies provide further in vivo evidence for an acute interaction between TRH and kappa-opiates.

journal_name

Brain Res

journal_title

Brain research

authors

Bhargava HN,Thorat SN

doi

10.1016/0006-8993(93)90144-c

subject

Has Abstract

pub_date

1993-10-15 00:00:00

pages

120-4

issue

1

eissn

0006-8993

issn

1872-6240

pii

0006-8993(93)90144-C

journal_volume

625

pub_type

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