Effects of acute central LH-RH administration of the skin temperature response in morphine dependent rats.
There are numerous reports of a temporal relationship between LH secretion and a subsequent flushing response in menopausal women. We have developed a morphine-dependent animal model to study the mechanisms of the hot flush. Administration of naloxone to these animals results in a surge in LH secretion which precedes the elevation in tail skin temperature (TST). In the present study, we utilized central administration of an LH-RH agonist and antagonist to evaluate the skin temperature response in our animal model. Ovariectomized female rats were fitted with unilateral cannula in the lateral ventricle (LV). One week later these animals were midly restrained to allow for continuous measurement of tail skin temperatures (TST). Central administration of naloxone was without effect in controls but produced a 5-6 degree C rise of TST in the morphine-dependent rat while central administration of 10 microliters of the saline vehicle produced no changes in TST in either group. A similar increased sensitivity to LH-RH was observed in morphine-dependent rats. Administration of 5 or 10 micrograms of the LH-RH agonist (Des-Gly10, [im-Bzl-D-His6]LH-RH ethylamide) into the LV produced a significantly greater elevation in TST (4 degrees C) in the morphine-dependent rats compared to a negligible rise in TST in the control rats; however, administration of a larger dose of 20 micrograms of the LH-RH agonist produced similar TST responses of about 4 degrees C in both groups. Intravenous administration of the LH-RH agonist (10 micrograms) was ineffective in producing any temperature effect in morphine-dependent rats. Thus, it appears that the morphine-dependent rat is more sensitive to the LH-RH agonist and the temperature response is mediated by a central mechanism which is similar to that observed following administration of a dose of naloxone. In a subsequent study central administration of the LH-RH agonist (5 micrograms/10 microliters) resulted in a similar rise in serum LH in both control and morphine-dependent rats, suggesting that the elevation in TST is not closely associated with LH secretion. Further support for a role of LH-RH in our animal model was obtained following central administration of an LH-RH antagonist [( D-Phe2.6, Pro3]LH-RH) which blocked the rise in TST associated with systemic administration of naloxone (1 mg/kg, s.c.) in morphine-dependent rats.(ABSTRACT TRUNCATED AT 400 WORDS)
Katovich
M J
MJ
Department of Pharmacodynamics, College of Pharmacy, JHMHC, University of Florida, Gainesville 32610.
Simpkins
J W
JW
O'Meara
J
J
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D002979:Climacteric / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D009020:Morphine; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D007987:Gonadotropin-Releasing Hormone; D009270:Naloxone; D009020:Morphine