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The brain 5‐HT 4 receptor binding is down‐regulated in the Flinders Sensitive Line depression model and in response to paroxetine administration
Author(s) -
Licht Cecilie L.,
Marcussen Anders B.,
Wegener Gregers,
Overstreet David H.,
Aznar Susana,
Knudsen Gitte M.
Publication year - 2009
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 - 10.1111/j.1471-4159.2009.06050.x
Subject(s) - paroxetine , 5 ht receptor , endocrinology , receptor , medicine , serotonin , antidepressant , 5 ht1a receptor , hippocampus , citalopram , chemistry , pharmacology , biology
The 5‐hydroxytryptamine (5‐HT 4 ) receptor may be implicated in depression and is a new potential target for antidepressant treatment. We have investigated the brain 5‐HT 4 receptor [ 3 H]SB207145 binding in the Flinders Sensitive Line rat depression model by quantitative receptor autoradiography, and related this to 5‐HT transporter ( S )‐[ N ‐methyl‐ 3 H]citalopram binding. We also determined the regulation of 5‐HT 4 receptor binding by 1, 14, and 21 days of paroxetine administration and subchronic 5‐HT depletion, and compared this with changes in 5‐HT 2A receptor [ 3 H]MDL100907 binding. In the Flinders Sensitive Line, the 5‐HT 4 receptor and 5‐HT transporter binding were decreased in the dorsal and ventral hippocampus, and the changes in binding were directly correlated within the dorsal hippocampus. Chronic but not acute paroxetine administration caused a 16–47% down‐regulation of 5‐HT 4 receptor binding in all regions evaluated including the basal ganglia and hippocampus, while 5‐HT depletion increased the 5‐HT 4 receptor binding in the dorsal hippocampus, hypothalamus, and lateral globus pallidus. In comparison, the 5‐HT 2A receptor binding was decreased in the frontal and cingulate cortices after chronic paroxetine administration, and markedly reduced in several regions after 5‐HT depletion. Thus, the 5‐HT 4 receptor binding was decreased in the Flinders Sensitive Line depression model and in response to chronic paroxetine administration.