Repeated treatment with antidepressants differentially alters 5-HT1A agonist-stimulated [35S]GTPγS binding in rat brain regions

被引:74
作者
Shen, C [1 ]
Li, H [1 ]
Meller, E [1 ]
机构
[1] NYU, Sch Med, Dept Psychiat, Millhauser Labs, New York, NY 10016 USA
关键词
autoradiography; receptor-G protein coupling; hippocarnpus; dorsal raphe; lateral septum;
D O I
10.1016/S0028-3908(02)00064-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Electrophysiological studies have led to the proposal that the neurobiological mechanism(s) underlying drug therapy of anxiety and depression involve(s) regionally specific adaptations in 5-HT1A receptor sensitivity. Depending on the drug utilized, a decrease in sensitivity of inhibitory somatodendritic autoreceptors, an increase in sensitivity of postsynaptic receptors, or both alterations, occur after several weeks of treatment. This hypothesis was tested using N,N-dipropyl-5-carboxamidotryptamine-stimulated guanosine-5'-O-(3-thio)triphosphate ([S-35]GTPgammaS) binding assessed by autoradiography. Rats were treated for 21 days with one of four different anxiolytic/antidepressant drugs (in mg/kg): fluoxetine (10), imipramine (10), clorgyline (1), ipsapirone (2 x 20) or saline. Three brain regions rich in 5-HT1A receptors were examined: the dorsal raphe (somatodendritic), the dorsal hippocampus (postsynaptic) and the lateral septum (postsynaptic). Only imipramine (+17%) and fluoxetine (+54%) significantly increased agonist-stimulated binding in the dorsal hippocampus; all drugs except imipramine significantly decreased binding in the dorsal raphe (-19 to -41%). These results generally support the concept of a net enhancement of hippocampal 5-HT neurotransmission via one or more 5-HT receptor subtypes. The most consistent effect, however, was a significant decrease in stimulated [S-35]GTPgammaS binding in the lateral septum after all four treatments (-14 to -23%), suggesting that this may be a heretofore unrecognized common outcome of antidepressant treatment deserving further study. (C) 2002 Elsevier Science Ltd. All rights reserved.
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页码:1031 / 1038
页数:8
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