LONG-LATENCY RESPONSES OF BRAIN NORADRENERGIC NEURONS TO NOXIOUS STIMULI ARE PREFERENTIALLY ATTENUATED BY INTRAVENOUS MORPHINE

The nucleus locus coeruleus (LC) has been strongly implicated in the p rocessing of noxious stimuli. Consistent with this, previous studies h ave shown that spontaneous LC discharge is depressed by morphine. Howe ver, effects of morphine on evoked responses of LC neurons to noxious stimuli have not been systematically examined. We reported recently th at responses to footshock stimuli in rat locus coeruleus neurons consi st of an early (A-fiber mediated) component and a previously undescrib ed late (C-fiber mediated) component. In the present study, we adminis tered analgesic doses of morphine (0.1, 0.5, or 1.0 mg/kg, i.v.) to de termine the effect on A- and C-fiber components of footshock responses in LC neurons. Doses of 0.5 and 1.0 mg/kg significantly attenuated th e C-fiber mediated response of LC neurons without affecting the A-fibe r response component. Spontaneous LC discharge was reduced by administ ration of all doses of morphine. Both depressive effects of morphine w ere abolished by intravenous administration of naloxone. In contrast, local microinfusion of naloxone into the LC abolished the morphine-ind uced decrease of spontaneous discharge but did not prevent the depress ion of the C-fiber mediated footshock response by morphine. This indic ates that the site of action for morphine's attenuation of the late LC response to footshock stimulation is outside of the LC. The results a re consistent with the hypothesis that the late (C-fiber-mediated) foo tshock responses in locus coeruleus are involved in the processing of noxious stimuli and may contribute to anti-nociceptive mechanisms.