ROLE OF NEUROTENSIN IN THE NUCLEUS RAPHE MAGNUS IN OPIOID-INDUCED ANTINOCICEPTION FROM THE PERIAQUEDUCTAL GRAY

These studies examined the role of the neurotensinergic projections ex tending from the periaqueductal gray (PAG) to the nucleus raphe magnus (NRM) on the inhibition of the tail-flick reflex produced by microinj ection of morphine or beta-endorphin in the PAG. Neurotensin (3-30 nmo l) or the partial agonist [D-Trp11] neurotensin (100 and 300 pmol) mic roinjected into the NRM of awake rats produced a dose-dependent inhibi tion of the tail-flick response lasting 90 to 150 min. Lower doses of neurotensin (0.03-0.3 nmol) produced a hyperreflexive tail-flick respo nse 10 min after injection, which correlated with a decreased hot plat e latency. Additionally, a dose of [D-Trp11]neurotensin (3 pmol) that had no intrinsic activity antagonized both the antinociceptive as well as hyperreflexive responses of neurotensin. Morphine (6 nmol) injecte d into the PAG produced an inhibition of the tail-flick response that was enhanced by injection Of [D-Trp11]neurotensin (3 pmol) into the NR M. In contrast, injection Of [D-Trp11]neurotensin (3 pmol) into the NR M had no effect on the inhibition of the tail-flick produced by beta-e ndorphin (10 nmol) in the PAG. Antineurotensin antiserum yielded resul ts similar to those obtained with [D-Trp11]neurotensin. Although neuro tensin was found to produce changes in tail skin temperature, it was p ossible to dissociate these effects from changes in tail-flick latency . These data suggest that neurotensin produces both antinociceptive an d hyperalgesic responses when injected into the NRM. Furthermore, neur otensin containing neuronal projections from the PAG to the NRM differ entially mediate the responses to morphine and beta-endorphin in the P AG, as morphine's action appears to involve the antianalgesic componen t of neurotensin in the NRM, whereas beta-endorphin's does not.