NEUROTENSIN EXCITATION OF SEROTONERGIC NEURONS IN THE DORSAL RAPHE NUCLEUS OF THE RAT IN-VITRO

Neurotensin-containing terminals and radioligand binding sites are pre sent in the dorsal raphe nucleus. The purpose of this study was to tes t, in brain slices containing this nucleus, the effect of neurotensin on the electrical activity of serotonergic neurons. In extracellular r ecordings, the cells were identified by the ability of the al-adrenoce ptor agonist phenylephrine to induce firing, and serotonin to reduce t his effect. After washout of phenylephrine, neurotensin (10 nM to 10 m u M) induced a concentration-dependent increase in the firing rate of serotonergic neurons (EC(50) = 142 nM; maximum effect similar to 1 mu M). The neurotensin excitation, which was mimicked by neurotensin frag ments 8-13 but not neurotensin peptide fragment 1-8 and selectively bl ocked by SR 48692 (100 nM), was observed mainly in the ventral part of the nucleus, Most serotonergic neurons showed marked desensitization to neurotensin, even at low concentrations. The neurotensin response w as occluded by supramaximal concentrations of phenylephrine. In intrac ellular recordings using KCl-containing electrodes, neurotensin induce d an inward current associated in some cases with a decrease in appare nt input conductance. In conclusion, neurotensin was found to have an excitatory action on serotonergic neurons in the ventral part of the d orsal raphe nucleus, an effect which could be subject to desensitizati on and was occluded by phenylephrine. This occlusion phenomenon may be important for the physiological role of neurotensin in the dorsal rap he nucleus.