Thermogenic effects of dihydrocodeine in the rat.
The object of this study was to assess the effects of dihydrocodeine on thermogenesis and brown adipose tissue activity in the rat from measurements of oxygen consumption and blood flow. Acute injection of dihydrocodeine tartrate (s.c.) stimulated resting oxygen consumption (VO2) in Sprague-Dawley rats in a dose-dependent manner (0.5-50 mg/kg), with a peak response (40-45% increase) occurring at 10-25 mg/kg. This effect was also observed in urethane-anaesthetized rats (although the effect was reduced) and in conscious animals following gastric intubation with the drug. Pretreatment of rats with either a beta-adrenergic antagonist (propranolol, 20 mg/kg), ACTH (4 g/kg), or an opiate antagonist (WIN44441-1, 2 mg/kg) significantly reduced the response to dihydrocodeine, whereas corticosterone injection (5 mg/kg) enhanced the effect. Surgical adrenalectomy or hypophysectomy (HYPX) almost completely abolished the thermogenic effect of dihydrocodeine. Dihydrocodeine also stimulated VO2 in lean (58% increase) and genetically obese Zucker rats (69% increase), and in both Zucker genotypes these responses were only slightly affected by HYPX, but enhanced in HYPX rats treated daily with corticosterone (1 mg/kg). Tissue blood flow, assessed from the distribution of radiolabelled microspheres, was unaffected in white adipose tissue, skeletal muscle, testes, kidney, brain, and liver (arterial supply) after a single injection of dihydrocodeine (25 mg/kg), but flow to interscapular and perirenal brown adipose tissue was increased by 9- to 10-fold. Surgical sympathectomy of brown adipose tissue prevented the increase in blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Rothwell
N J
NJ
Department of Physiology, St. George's Hospital Medical School, Tooting, London, U.K.
Stock
M J
MJ
Tedstone
A E
AE
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D003061:Codeine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011924:Rats, Zucker; D012039:Regional Blood Flow / Q000187:drug effects
C014481:dihydrocodeine; D003061:Codeine