Serotonin depletion in the dorsal and ventral hippocampus: Effects on locomotor hyperactivity, prepulse inhibition and learning and memory

We present an overview of our studies on the differential role of serotonergic projections from the median raphe nucleus (MRN) and dorsal raphe nucleus (DRN) in behavioural animal models with relevance to schizophrenia. Stereotaxic microinjection of the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the MRN or one of its main projections regions, the dorsal hippocampus, induced a marked enhancement of phencyclidine-induced locomotor hyperactivity and a disruption of prepulse inhibition (PPI) in rats. There was no enhancement of locomotor hyperactivity induced by amphetamine or MK-801 or after 5,7-DHT lesions of the DRN or ventral hippocampus. Rats with dorsal hippocampus lesions did not show significant changes in the Y-maze test for short-term spatial memory, the Morris water maze for long-term spatial memory, or in the T-maze delayed alternation test for working memory. These chronic lesion studies suggest a modulatory influence of serotonergic projections from the MRN to the dorsal hippocampus on phencyclidine effects and prepulse inhibition, but not on different forms of learning and memory. The results provide new insight into the role of serotonin in the dorsal hippocampus in aspects of schizophrenia.