Morphine Effects on Locus Ceruleus Neurons Are Dependent on the State of Arousal and Availability of External Stimuli: Studies in Anesthetized and Unanesthetized Rats

Because the physiological characteristics of noradrenergic locus ceruleus (LC) neurons differ in anesthetized and unanesthetized rats, the effects of morphine on LC activity recorded in both conditions were compared. Intracerebroventricular administration of morphine inhibited spontaneous LC discharge of both anesthetized and unanesthetized rats but morphine was at least 10 times more potent in anesthetized rats. In anesthetized rats LC discharge evoked by sciatic nerve stimulation was insensitive to doses of morphine (0.03 or 0.1 microgram) that inhibited LC spontaneous activity. Only the highest dose of morphine (0.3 microgram) which inhibited completely tonic activity decreased significantly evoked discharge. In parallel experiments in unanesthetized rats, the presentation of auditory stimuli evoked a pattern of LC discharge similar to that evoked by sciatic nerve stimulation in anesthetized rats. Morphine (1.0 and 3.0 micrograms) decreased both spontaneous and evoked activity in these rats; however, spontaneous LC discharge was more sensitive to morphine, as was observed with anesthetized rats. Quantitative analyses of these effects indicated that morphine tends to alter the pattern of LC discharge to sensory stimuli such that the signal-to-noise ratio (ratio of evoked/tonic activity during stimulus presentation) is increased. Morphine effects were reversed by naltrexone (1.0 mg/kg s.c.) in anesthetized rats and 1.0 microgram i.c.v. in unanesthetized rats. The present results indicate that the degree of arousal and the availability of environmental stimuli are important determinants of opiate effects on LC activity.