Differential roles of the adrenal gland in the suppression of morphine antinociceptive tolerance development by alpha- and beta-adrenergic blockers.
Concomitant treatment with phentolamine, an alpha-blocker, or with propranolol, a beta-blocker, suppressed the development of morphine tolerance in sham-operated (Sham) mice. In adrenalectomized (ADX) mice, daily morphine developed tolerance as well as in the Sham group, and concurrent phentolamine suppressed the development of tolerance, whereas such suppression by propranolol was abolished. Supplemental treatment of ADX mice with dexamethasone did not restore the suppressive effect of propranolol. These results suggest that different mechanisms underlie the prevention of tolerance development by alpha- and beta-blockers, and that adrenal cortex does not seem to participate in the suppression by beta-blockers.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki University, Japan.
M
M
Takahashi
T
T
Okada
H
H
Kaneto
D000311:Adrenal Glands / Q000502:physiology*; D000315:Adrenalectomy; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000700:Analgesics; D009020:Morphine; D003907:Dexamethasone; D011433:Propranolol; D010646:Phentolamine