In previous works we studied, on cats, the effects of lateral habenula (LH) stimulation on hippocampal units. In particular, the results showed an excitation or an inhibition in relation to the stimulation frequency (0.5-3.0 Hz or 5.0-20 Hz, respectively). All the LH stimulation effects were antagonised by iontophoretic intrahippocampal application of methysergide (MS). In this series of experiments it was possible to demonstrate, on rats, that LH stimulation causes an excitatory effect in a major number of hippocampal units in relation to the frequency increase. The inhibitory effect by iontophoretic serotonine application and the reversible blockade of habenular modulation after iontophoretic methysergide administration on hippocampal units suggest, on rats, the involvement of raphe. Such hypothesis, with anatomical evidences demonstrating an excitatory projection between LH and raphe, was confirmed by data concerning the effects of intraraphal NMDA iontophoretic application on hippocampal units (NMDA application for 30 s = excitation; NMDA administration for 10-15 min = inhibition). All the results suggest an habenular modulation of hippocampus through the involvement of the raphe in the context of which an interneurone is inhibitory on the efferent serotonergic raphe-hippocampus projection. This hypothesis finds further support from MS blockade effect during intraraphal NMDA iontophoretic administration.

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