Modification of rat thermal responses to morphine by alpha-FMH suggests a role for neural histamine in morphine tolerance.
In rats, morphine may either raise or lower body temperature depending on the dose. A morphine dose of 50 mg/kg, i.p., consistently produced a nearly maximal hypothermic response in non tolerant rats, whereas this dosage induced an elevation of body temperature in tolerant rats. In rats pretreated with alpha-fluoromethylhistidine (alpha-FMH), an irreversible inhibitor of histidine decarboxylase which induces a reduction in brain histamine synthesis, this morphine dose of 50 mg/kg, i.p. produced an elevation of rectal temperature resembling that observed in morphine-tolerant rats. To confirm the suggestion that hyperthermic effects of the higher dose of morphine in morphine-tolerant rats or in alpha-FMH-pretreated rats could be related to a possible involvement of mediators of fever, e.g. prostaglandins, animals were pretreated with acetylsalicylic acid (aspirin, Bayer) 30 mg/kg, i.p., 60 min before morphine. Results showed that acetylsalicylic acid prevented the hyperthermic response of morphine, resulting in a fall in body temperature. Since morphine releases histamine and alpha-FMH inhibits histamine synthesis, our data demonstrating that an inhibitor of prostaglandin-synthetase showed efficacy only in animals responding with fever to the higher dose of the opiate, suggests a physiological antagonism between histamine and prostaglandins on mechanisms underlying hyper/hypothermic responses to morphine.
Arrigo-Reina
R
R
Institute of Pharmacology and Pharmacognosy, Faculty of Pharmacy, University of Catania, Italy.
Spadaro
C
C
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects*; D004361:Drug Tolerance; D006632:Histamine / Q000502:physiology*; D006639:Histidine / Q000031:analogs & derivatives*; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D008762:Methylhistidines; D006639:Histidine; C028309:alpha-fluoromethylhistidine; D009020:Morphine; D006632:Histamine; D001241:Aspirin