As one of the most important diffused brain modulatory systems, the nucleus locus coeruleus (LC) receives most of its afferents from the nucleus paragigantocellularis (PGi) and plays a major role in the control of drug dependence and some emotional and exciting states. For detailed investigation of the effect of morphine on relationship between these two brain stem nuclei, the activity of the rat (Sprague-Dawley) LC neurons was examined after being dependent on morphine in comparison with independent group. The activity of the nucleus LC neurons with and without the activity of nucleus PGi neurons was recorded using extracellular single unit recording technique. Lidocaine microinjection (1 ml, in 1-2 min, 2.5%) was used for inactivation of PGi. The PSTH (Peri-Stimulus Time Histogram) of the neuronal activity showed a decrease in neuronal firing rate of LC by 85.8±1.7% in morphine-dependent group (from 2.95 spike/sec to 0.64 spike/sec, n = 4) and by 48.3±4.3% (from 3.5 spike/sec to 1.94 spike/sec, n = 6) for independent one. The difference was significant (P<0.001). The time period of the decrease in activity was 120±9 min for dependent group and 44.8±4.5 min for independent one. The difference was also significant (P<0.001). It seems likely that development of morphine dependence entails some changes in neurons of the nucleus LC, which may cause an increase in its neuronal firing rate in the presence of nucleus PGi neuronal activity.