Activation of central mu-opioid receptors is involved in clonidine analgesia in rats.
The analgesic effect of clonidine in spontaneously hypertensive rats (SHR) and in normotensive Sprague-Dawley (SD) rats was assessed by using the formalin pain test. The analgesic response of SD rats to low doses (15-60 micrograms/kg i.p.) but not to a high dose (150 micrograms/kg i.p.) of clonidine was inhibited by naloxone, 2 mg/kg i.p., and similar interaction was noted in SHR. In both rat strains, the analgesic response to low i.p. doses of clonidine was also inhibited by injection of 5 micrograms of naloxone or 7 micrograms of beta-funaltrexamine, a mu-receptor antagonist, into the lateral cerebral ventricle. I.c.v. injection of 5 micrograms of ICI 174864, a delta-receptor antagonist, potentiated or did not influence clonidine analgesia in SD rats and SHR, respectively. It is concluded that the analgesic response to clonidine involves activation of central mu-opioid receptors in both SHR and SD rats, possibly by an endogenous opioid released by clonidine.
Mastrianni
J A
JA
Department of Pharmacology, McGill University, Montreal, Que., Canada.
Abbott
F V
FV
Kunos
G
G
D000698:Analgesia; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011919:Rats, Inbred Strains / Q000378:metabolism*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu; D013045:Species Specificity
D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009270:Naloxone; D004743:Enkephalin, Leucine; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D003000:Clonidine