Analgesia and increases in limbic and cortical MOPEG-SO4 produced by periaqueductal gray injections of morphine.

Abstract

Analgesia and changes in limbic and cortical concentrations of the major brain noradrenaline metabolite, 3-methoxy-4-hydroxy-phenylethylene glycol sulphate (MOPEG-SO4), were investigated in rats following the bilateral injection of morphine into the periaqueductal gray (PAG). Morphine, at a dose of 5 micrograms per bilateral site, produced a significant antinociceptive effect within 15 min of injection. This effect, as measured by the tail flick analgesic test, remained constant at a level of approximately 75% of the maximum for 60 min. Significant increases in limbic and cortical MOPEG-SO4 were also observed 15, 30 and 60 min after the 5 micrograms bilateral PAG injection of morphine. However, MOPEG-SO4 concentrations exhibited a sharp peak in both brain areas at 30 min. Analgesia and the regional increases in MOPEG-SO4 were antagonized by the prior systemic injection of naloxone (1 mg kg-1, i.p.). Thus, analgesia and increases in noradrenaline metabolism in two brain regions appear to be mediated by the specific activation of opiate receptors in the PAG. Although these findings indicate that brain noradrenergic systems may be involved in the mediation of morphine analgesia, the lack of a strict temporal relationship between antinociceptive action and increases in MOPEG-SO4, suggests that analgesia cannot be totally attributed to changes in brain noradrenergic transmission.