MORPHINE ANALGESIA IN THE FORMALIN TEST - REVERSAL BY MICROINJECTION OF QUATERNARY NALOXONE INTO THE POSTERIOR HYPOTHALAMIC AREA OR PERIAQUEDUCTAL GRAY

Bilateral microinjection of 5 nmol morphine into the posterior hypotha lamic area (PHA), periaqueductal gray matter (PAG) or ventral tegmenta l area (VTA) elicits powerful suppression of nociceptive behaviors in the formalin test, an animal model of injury produced pain. The object of the present study was to determine whether analgesia in the formal in test (50 mu l 2.5% formalin injected s.c. in one hindpaw) induced b y systemically administered morphine requires opioid action at these s ites, or other putative sites of opioid action. Morphine sulphate (6 m g/kg s.c.) produced almost complete analgesia in the second phase of t he formalin test (30-50 min after formalin). Bilateral microinjection of the quaternary opioid antagonist naloxone methobromide (NxBr, 28 ng in 0.5 mu l, 22 min after morphine) into the PHA completely abolished morphine analgesia, while NxBr into FAG partially reversed analgesia. Microinjection of NxBr into the VTA, central nucleus of the amygdala, habenula, striatum, nucleus accumbens or hypothalamic sites outside t he PHA did not antagonize morphine analgesia, although microinjections into some of these sites appeared to reduce the cataleptogenic effect s of morphine. The data indicate that the PHA and FAG are probably the primary sites of action of morphine in the formalin test. (C) 1998 El sevier Science B.V. All rights reserved.