The spontaneous withdrawal from morphine in morphine-dependent rats significantly decreased the duration of active interaction in social interaction test and the number of licks during the shock-punished period in Vogel's conflict procedure, which were attenuated by buspirone, a 5-HT1A agonist, as well as para-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase. Naltrexone (NTX), a potent opioid receptor antagonist, also dose- and time-dependently reduced both indices mentioned above, which was blocked by morphine or PCPA and was enhanced by 5-hydroxytryptophan, a precursor of 5-HT. In the test of neurotransmitter releases in rat brain slices, both morphine-withdrawal and NTX enhanced high potassium(30mM)-induced 5-HT release in slices of the area of the raphe nucleus. These results suggested that both morphine-withdrawal and NTX produced anxieties in morphine-dependent and normal rats, respectively, which were mediated by the central 5-HTergic neurotransmission. Central opioidergic neurons inhibited 5-HTergic neurons tonically and presynaptically. Such an effect was reduced or blocked by NTX, or during morphine-withdrawal, and 5-HTergic neurons were disinhibited, leading to a state of anxiety.