Physostigmine-induced hypothermic response in rats and its relationship with endogenous arginine vasopressin.
OBJECTIVE
It is well known that physostigmine (PHY) and other anticholinesterase (anti-ChE) agents induce hypothermia in rodents but little is known about the mechanism of action. Because arginine vasopressin (AVP) has been found to be an endogenous antipyretic molecule in the CNS, we determined if PHY-induced hypothermia is linked to the endogenous release of AVP.


METHODS
Core temperature and motor activity were monitored by telemetry in rats maintained at an ambient temperature of 25 degrees C. Tail skin temperature was also measured at 30min intervals to estimate nonevaporative heat loss. The central cholinergic antagonist, scopolamine (1mg/kg; ip) and an AVP V(1) receptor antagonist (30microg/kg; ip) were administered during the period of PHY (200microg/kg; sc) induced hypothermia at 10am. Plasma AVP concentration and plasma cholinesterase (ChE) activity were measured at 50min after administration of PHY or scopolamine, respectively.


RESULTS
PHY led to a rapid reduction in core temperature concomitant with a marked increase in heat loss from the tail. The hypothermic response of PHY was blocked by the AVP V(1) receptor antagonist. Administration of scopolamine also reversed the hypothermic responses and led to marked elevations in motor activity. Plasma AVP levels increased markedly at 50min after PHY and plasma ChE activity was significantly reduced by PHY.


CONCLUSIONS
The results clearly demonstrate that PHY-induced hypothermia was blocked by the AVP V(1) antagonist and associated with elevations in plasma AVP, suggesting a novel role for AVP in the mechanism of action of anti-ChE agents.
Yang
Yong-Lu
YL
Department of Physiology, Chengdu Medical College, Chengdu, Sichuan 610083, People's Republic of China. ylyang9@sohu.com
Shen
Zi-Ling
ZL
Zou
Qiang
Q
Tang
Yu
Y
Huang
Tao
T
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D001833:Body Temperature Regulation / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002802:Cholinesterases / Q000097:blood; D005260:Female; D007035:Hypothermia / Q000097:blood / Q000139:chemically induced* / Q000201:enzymology / Q000517:prevention & control; D009043:Motor Activity / Q000187:drug effects; D010830:Physostigmine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology; D012881:Skin Temperature / Q000187:drug effects; D013686:Telemetry; D013997:Time Factors
D065092:Antidiuretic Hormone Receptor Antagonists; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D001127:Arginine Vasopressin; D010830:Physostigmine; D012601:Scopolamine; D002802:Cholinesterases