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Selective blockade of neurokinin (NK) 1 receptors facilitates the activity of adrenergic pathways projecting to frontal cortex and dorsal hippocampus in rats
Author(s) -
Millan Mark J.,
Lejeune Françoise,
De Nanteuil Guillaume,
Gobert Alain
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00211.x
Subject(s) - locus coeruleus , endocrinology , medicine , hippocampus , receptor , antagonist , adrenergic , chemistry , serotonin , blockade , biology , central nervous system
The selective NK 1 receptor antagonist, GR205,171 (2.5–40.0 mg/kg, i.p.), dose‐dependently elevated dialysate levels of noradrenaline (NA), but not serotonin (5‐HT), in the frontal cortex of freely moving rats. This action was exerted stereospecifically inasmuch as its less active isomer, GR226,206, was ineffective. In the dorsal hippocampus, GR205,171 (but not GR226,206) also significantly increased dialysate levels of NA, whereas levels of 5‐HT were unaffected. Further, in anaesthetized rats, GR205,171 dose‐dependently (1.0–4.0 mg/kg, i.v.) increased the firing rate of adrenergic perikarya in the locus coeruleus. In contrast, their activity was not modified by GR226,206. These findings indicate that selective blockade of NK 1 receptors enhances the activity of ascending adrenergic pathways in rats. Adrenergic mechanisms may, thus, be involved in the potential antidepressant and other functional properties of NK 1 receptor antagonists.