Excitatory action of the mesolimbic dopamine system on septal neurones.

Fluorescence histochemical studies have demonstrated a topographical distribution of dopaminergic nerve terminals in limbic forebrain and cortical regions4, 9-11. These data, together with biochemical evidence indicating significant amounts of dopamine (DA) in these regionsl,XS, zl, suggest the existence of a major anatomical pathway projecting to forebrain areas which originate in mesencephalic tegmental regions known to be rich in DA cell bodies3,10, 29. Of particular interest in the present study is the catecholaminergic innervation of the septal area, which has previously been considered to consist almost exclusively of noradrenergic nerve terminals 14. More recently histochemical mapping experiments 9, have demonstrated a high density of DA terminals in the medial aspect of the lateral septal region which remain after bilateral transection of the ascending noradrenergic projection. Lindvall 9 has shown that transection of the medial forebrain bundle at the level of the rostral substantia nigra, or bilateral electrolytic lesions of the A10 mesencephalic cell group (according to Dahlstr6m and Fuxe 3) result in a complete loss of septal DA terminals. These data suggest a direct dopaminergic fibre system innervating the lateral septal area which originates in the Al0 region of the ventromedial tegmentum. The present experiments were undertaken to further delineate the cells of origin of this pathway using retrograde axonal transport of horseradish peroxidase (HRP). The possibility that DA may be involved as a synaptic transmitter in this projection system was determined by observing (1) the change in septal cell discharge elicited by A10 stimulation and (2) the effects of 6-hydroxydopamine (6-OHDA) and the DA receptor blocking agent haloperidol on the synaptically evoked response patterns. In order to demonstrate the cells of origin of afferent projections to the septal area, 0.1-0.3 #1 of a 33 ~ solution of horseradish peroxidase (HRP, Type VI, Sigma Chemical) in saline was injected stereotaxically into either the lateral or medial septal region of 11 male Wistar rats anaesthetized with Nembutal (50 mg/kg i.p.). Following survival periods of 24 h the rats were killed, perfused and frozen sections cut and treated to reveal peroxidase activity according to methods described previously 1~. The