Central serotonin (5-HT) is an important neuromodulator for regulating numerous physiological and behavioural activities. Its deficiency is believed to be responsible for the development of mental disorders such as anxiety, depression and posttraumatic stress disorder (characterized by abnormal fear memories), but the underlying neural mechanisms remain largely unclear. And recent studies have demonstrated contradictory findings on the roles of central 5-HT in these physiological process. To study the function of 5-HT in the physiological and behavioral processes, we generated conditional knockout mice in which transcription factor Lmx1b was inactivated specifically in raphe nuclei to prevent the development of central 5-HT neurons and examined their anxiety, spatial memory, contextual fear memory and morphine addiction behaviour. In the present studies, we found that central 5-HT deficient mice showed normal spatial learning but impaired spatial memory in Morris water maze test. Surprisingly, central 5-HT deficient mice showed reduced anxiety-like behaviours in light-dark choice, elevated-plus maze and novelty-suppressed feeding tests. Contextual fear memory of central 5-HT deficient mice was stronger than that of wild type mice and this enhanced fear memory was attenuated by giving 5-HT or DPAT in vivo. Further electrophysiological studies in hippocampal slices showed that foot-shock-induced suppression of LTP and induction of LTD were not observed in central 5-HT deficient mice, which was rescued by bath application of 5-HT or DPAT in vitro, suggested that the alteration of hippocampal synaptic plasticity is caused by loss of central 5-HT. Moreover, morphine addictive behaviour of central 5-HT deficient mice became markedly endurable and LTP induction in hippocampal slices of central 5-HT deficient mice was more enhanced than that of WT mice after morphine sensitization. Our findings indicate that genetic removal of central 5-HT neurons in mice results in a reduction of anxiety-like behaviour and impaired spatial memory but an increase of contextual fear memory and morphine addictive behaviour. As hippocampus has a key role in the formation and maintenance of spatial memory and contextual fear memory, we propose that the altered hippocampal synaptic plasticity may contribute to these aberrant behaviours.