Mechanisms mediating the thermal response to morphine withdrawal in rats.
Studies were undertaken to evaluate the role of peripheral adrenergic mechanisms and the adrenal gland in the thermal responses which accompany morphine withdrawal in the rat. Ovariectomized rats were addicted to morphine and subsequently withdrawn by administration of naloxone. This treatment resulted in a significant rise (5-6 degrees C) in tail skin temperature (TST) and fall in colonic temperature (2-4 degrees C). Systemic administration of clonidine (0.5 mg/kg) completely suppressed this surge in TST and significantly attenuated the fall in core temperature. Similar results were observed following the systemic administration of ST-91, another alpha 2-adrenergic agonist which does not cross the blood-brain barrier. Central administration of ST-91 (50 micrograms/5 microliters, icv) was also successful in attenuating these temperature changes in the morphine-dependent rat. Adrenalectomy and peripheral administration of propranolol (10 mg/kg sc) both resulted in a significant attenuation of the surge in TST and the fall in core temperature in the morphine-dependent rat which suggest some peripherally mediated event is necessary to produce the full skin temperature surge. Collectively, the data suggest a role for the adrenal gland and adrenergic receptors in producing the surge in TST in morphine-dependent rats. It also suggests that the blocking effects of the alpha 2-adrenergic agonist can be mediated both centrally and peripherally.
Katovich
M J
MJ
Department of Pharmacodynamics, College of Pharmacy University of Florida, Gainesville 32610.
Pitman
D L
DL
Barney
C C
CC
D000311:Adrenal Glands / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D012881:Skin Temperature; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D011941:Receptors, Adrenergic; D009270:Naloxone; C011266:ST 91; D009020:Morphine; D011433:Propranolol; D003000:Clonidine