title: Electrophysiological effects of neurotensin on dopaminergic neurones of the ventral tegmental area of the rat in vitro.
abstract: The effects of neurotensin on the spontaneous firing rate of presumed dopaminergic neurones of the ventral tegmental area of the rat, were studied in a slice preparation of brain by extracellular single-cell recordings. Bath-applied neurotensin excited all cells which were studied (N = 25). This effect was concentration-dependent; the threshold was 10(-10) M and maximal activation (about 30 spikes/10 sec) was obtained with 10(-6) M. The EC50 (half-maximal effective concentration) was roughly estimated at 35 nM. The action of neurotensin was mimicked by neurotensin 8-13 (N = 6), but not neurotensin 1-8 (N = 6). It persisted in low-calcium, high-magnesium solutions (N = 5) and therefore probably resulted from a direct activation of neurotensin receptors. The responses to neurotensin were long-lasting (30-60 min after a 10 min 10(-7) M infusion) and exhibited little tachyphylaxis. Dose-response curves to the dopaminergic agonist BHT920 showed that, during the infusion of 10(-7) M neurotensin, dopaminergic autoreceptors of some neurones were less sensitive than in control conditions. This was not a non-specific effect produced by the excitation, since it was not observed during the infusion of another excitant, N-methyl-D-aspartate (NMDA). These results show that neurotensin potently activates presumed dopaminergic neurones in the ventral tegmental area in vitro; it may also decrease the effectiveness of the autoreceptors of some neurones.
authors.affiliation: Department of Pharmacology, University of Liège, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Seutin
authors.forename: L
authors.initials: L
authors.lastname: Massotte
authors.forename: A
authors.initials: A
authors.lastname: Dresse
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009496:Neurotensin / Q000494:pharmacology*; D010446:Peptide Fragments / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D001381:Azepines; D010446:Peptide Fragments; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D009496:Neurotensin; C024763:talipexole; D004298:Dopamine