Neurotensin excitation of serotonergic neurons in the dorsal raphe nucleus of the rat in vitro.
Neurotensin-containing terminals and radioligand binding sites are present in the dorsal raphe nucleus. The purpose of this study was to test, in brain slices containing this nucleus, the effect of neurotensin on the electrical activity of serotonergic neurons. In extracellular recordings, the cells were identified by the ability of the alpha 1-adrenoceptor agonist phenylephrine to induce firing, and serotonin to reduce this effect. After washout of phenylephrine, neurotensin (10 nM to 10 microM) induced a concentration-dependent increase in the firing rate of serotonergic neurons (EC50 = 142 nM; maximum effect approximately 1 microM). The neurotensin excitation, which was mimicked by neurotensin fragments 8-13 but not neurotensin peptide fragment 1-8 and selectively blocked 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 was occluded by supramaximal concentrations of phenylephrine. In intracellular recordings using KCl-containing electrodes, neurotensin induced an inward current associated in some cases with a decrease in apparent input conductance. In conclusion, neurotensin was found to have an excitatory action on serotonergic neurons in the ventral part of the dorsal raphe nucleus, an effect which could be subject to desensitization and was occluded by phenylephrine. This occlusion phenomenon may be important for the physiological role of neurotensin in the dorsal raphe nucleus.
Jolas
T
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Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508, USA.
Aghajanian
G K
GK
D000818:Animals; D001931:Brain Mapping; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009496:Neurotensin / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*
D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C079087:SR 48692; D010656:Phenylephrine; D012701:Serotonin; D009496:Neurotensin