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- Title
The brain 5-HT<sub>4</sub> receptor binding is down-regulated in the Flinders Sensitive Line depression model and in response to paroxetine administration.
- Authors
Licht, Cecilie L.; Marcussen, Anders B.; Wegener, Gregers; Overstreet, David H.; Aznar, Susana; Knudsen, Gitte M.
- Abstract
The 5-hydroxytryptamine (5-HT4) receptor may be implicated in depression and is a new potential target for antidepressant treatment. We have investigated the brain 5-HT4 receptor [3H]SB207145 binding in the Flinders Sensitive Line rat depression model by quantitative receptor autoradiography, and related this to 5-HT transporter ( S)-[ N-methyl-3H]citalopram binding. We also determined the regulation of 5-HT4 receptor binding by 1, 14, and 21 days of paroxetine administration and subchronic 5-HT depletion, and compared this with changes in 5-HT2A receptor [3H]MDL100907 binding. In the Flinders Sensitive Line, the 5-HT4 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-HT4 receptor binding in all regions evaluated including the basal ganglia and hippocampus, while 5-HT depletion increased the 5-HT4 receptor binding in the dorsal hippocampus, hypothalamus, and lateral globus pallidus. In comparison, the 5-HT2A 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-HT4 receptor binding was decreased in the Flinders Sensitive Line depression model and in response to chronic paroxetine administration.
- Subjects
SEROTONIN; RADIOLIGAND assay; LABORATORY rats; HIPPOCAMPUS (Brain); ANTIDEPRESSANTS; PAROXETINE; HYPOTHALAMUS; GLOBUS pallidus
- Publication
Journal of Neurochemistry, 2009, Vol 109, Issue 5, p1363
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2009.06050.x