Naloxone improves, and morphine exacerbates, experimental shock induced by release of endogenous histamine by...

In mice, fatal shock induced by release of endogenous histamine by compound 48/80 was reversed by the intracerebroventricular (i.c.v.) administration of the opiate antagonist naloxone (10-25 micrograms) but not by the systemic administration of the selective peripherally acting antagonist, naltrexone methyl bromide (1-5 mg/kg). Moreover, systemic or i.c.v. administration of morphine (25 mg/kg and 25 micrograms, respectively) exacerbated shock induced by compound 40/80. This effect was blocked by i.c.v. naloxone (10 micrograms) or naltrexone methyl bromide (10 micrograms) but not by systemic naltrexone methyl bromide (5 mg/kg). The pathogenic effect of i.c.v. morphine was blocked by the systemic administration of the opiate antagonist Win 44,441-3 (5 mg/kg) but not by its inactive (+) isomer, Win 44,441-2. The results suggest possible involvement of central opiate (endorphin) mechanisms in the pathophysiology of fatal histamine shock in mice.