ROLE OF MU-1 OPIOID RECEPTOR SUBTYPE ON MORPHINE-INDUCED ANTINOCICEPTION AGAINST RESPONSES TO MECHANICAL AND CHEMICAL NOXIOUS STIMULI IN MICE

We investigate which mu receptor mediated antinociception against murine responses to mechanical and chemical noxious stimuli, caused by intrathecal (i.t.) or intracerebroventricular (i.c.v.) administration of morphine. The antinociceptive effects of morphine were measured using the tail-pressure test for mechanical noxious stimuli and the formalin test for chemical noxious stimuli. Morphine produced dose-related and significant antinociceptive effects on responses to both mechanical and chemical stimuli. Pretreatment with naloxonazine, a mu-1 receptor-selective antagonist (35 mg/kg s.c.) 24 hr before testing antagonized the antinociceptive effect of morphine on responses to chemical stimuli to a greater extent than responses to mechanical stimuli. Thus, antinociception due to i.c.v. morphine with chemical stimuli (formal in-induced behavioral response) was more sensitive to naloxonazine antagonism than that due to i.t. morphine. The present results suggest that the antinociceptive activity of both i.t. and i.c.v. morphine on responses to chemical stimuli is mediated through the mu-1 receptor subtype (naloxonazine-sensitive sites), indicating the presence of mu-1 receptor subtypes not only in supraspinal sites but also in spinal sites.