Alpha-adrenergic mediation of the tail skin temperature response to naloxone in morphine-dependent rats.
Studies were undertaken to evaluate the role of central noradrenergic neurons in the tail skin temperature (TST) surge that accompanies morphine withdrawal in the rat. A 5 degrees C increase in TST and a 1-2 degrees C decrease in rectal temperature (Tr) was observed following administration of a dose of naloxone HCl (NAL, 1 mg/kg, s.c.) which precipitated withdrawal in morphine-dependent rats. Intracerebroventricular (i.c.v.) injection of clonidine HCl, a partial alpha 2-adrenergic agonist did not alter TST in morphine-dependent animals. However, clonidine (10 or 50 micrograms/rat, i.c.v.) given 10 min prior to the administration of NAL completely blocked the TST response to the opiate antagonist in the morphine-dependent animals. Although NAL and clonidine reduced Tr to a similar extent in morphine-dependent rats, their effects were not additive when the drugs were administered sequentially. Treatment with the alpha-adrenergic antagonist phentolamine (11.9 or 60 micrograms/rat, i.c.v.) failed to alter TST when administered alone, but the highest dose significantly reduced the TST response to naloxone in the morphine-dependent rat. In addition, phentolamine, at high doses only, moderately reduced Tr, but the alpha-adrenergic antagonist failed to modify the decline in Tr associated with NAL-precipitated morphine withdrawal. Collectively, these data indicate that brain noradrenergic neurons play a role in the TST surge which accompanies NAL-precipitated morphine withdrawal, and that the TST and Tr responses can be dissociated in the morphine-dependent rat.
Katovich
M J
MJ
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville 32610.
Simpkins
J W
JW
Barney
C C
CC
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D005260:Female; D009021:Morphine Dependence / Q000378:metabolism*; D009270:Naloxone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012881:Skin Temperature / Q000187:drug effects; D013623:Tail / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D009270:Naloxone; D003000:Clonidine; D010646:Phentolamine