Brain 5-HT2A receptors have been implicated in various behavioural and physiological processes including hippocampus-dependent learning and memory. To clarify the cellular localization and chemical identity of 5-HT2A receptor-immunoreactive (-ir) neurons in the rat septal complex and dorsal hippocampus, an immunofluorescence histochemical study was performed using a monoclonal antibody to the 5-HT2A receptor. Pretreatment with colchicine increased the number of 5-HT2A receptor-ir cell bodies, indicating that the 5-HT2A receptor protein undergoes microtubule-dependent anterograde transport in axons and dendrites. 5-HT2A receptor immunoreactivity was detected in septal cholinergic neurons, identified with an antiserum to the vesicular acetylcholine transporter (VAChT), and in GABAergic cell bodies in the medial septum/diagonal band of Broca, identified with antisera to glutamic acid decarboxylase (GAD) and the calcium-binding protein parvalbumin. In the dorsal hippocampus, 5-HT2A receptor immunoreactivity was demonstrated in cells located in the pyramidal cell layer (CA1-3) throughout the Ammon's horn and in the granular cell layer of the dentate gyrus. Furthermore, 5-HT2A receptor immunoreactivity was present in most hippocampal interneurons identified by the presence of GAD65, parvalbumin, calbindin D-28k, somatostatin and neuropeptide Y. In contrast, 5-HT2A receptor immunoreactivity was present in only a few interneurons containing cholecystokinin and calretinin immunoreactivity. The results suggest that serotonin acting on 5-HT2A receptors can modulate hippocampal functions via direct actions on hippocampal glutamatergic principal cells and indirectly via actions on hippocampal interneurons with different phenotypes as well as GABAergic and cholinergic septohippocampal neurons.
Copyright 2004 Elsevier B.V.