Introduction: Although tolerance to and dependence on opioids are characterized by excessive activity of cAMP pathway in some brain stem nuclei, the impact of morphine dependence on activity of cAMP pathway in paragigantocellularis nucleus (PGi), located in the rostral ventrolateral medulla, remains unclear. Therefore, the effect of adenyl cyclase activator forskolin on spontaneous firing rate of PGi neurons anp precipitation of withdrawal signs in morphine dependent rats was studied. Material and Methods: Electrophysiologic extracellular single unit activity was recorded from PGi of urethane anesthetized NMRI male rats (200-350 g). Forskolin (100 nM /300-400 nL / 3-4 min) was microinjected into PGi. To assess behavioral signs, frequency analysis was used. Results: The results showed that spontaneous PGi neuronal firing rate in morphine dependent rats was lower than that of control ones, which confirms the tolerance to morphine. Forskolin caused an increase in PGi neuronal firing rate in control rats and completely suppressed spohtaneousfiring rate of PGi neurons in morphine dependent ones (p<0.001). In freely moving control rats, forskolin induced wet-dog shake and chewing sings but not in morphine dependent ones. Conclusion: It is concluded that adaptive change in activity of cAMP pathway in PGi neurons following chronic morphine exposure may play a role in the development of tolerance to and dependence on morphine.