MadSci Network: Neuroscience |
Great question! Serotonin which is present in the extracellular (i.e., outside of a cell) space is actively transported into a cell. The process of taking the serotonin back into the cell is termed "reuptake". There are different reuptake mechanisms, or transporters, for different neurotransmitters- for example, serotonin and norepinephrine, which is also a neurotransmitter in the central nervous system, are transported by different proteins. Therefore, selective serotonin reuptake inhibitors (SSRIs) selectively inhibit the reuptake of serotonin. SSRIs are used clinically to treat depression. Drugs termed tricyclic antidepressants inhibit the reuptake of norepinephrine. These drugs are also used clinically as antidepressants. Both SSRIs and tricyclic antidepressants are described in standard pharmacology textbook, such as, Goodman & Gilman's "The Pharmacological Basis of Therapeutics" Tests to determine if a drug is an SSRI employ microdialysis. In this procedure a fluid is passed through a tissue (either in vivo using an immobilized animal or in vitro using an excised tissue). As the fluid passes through the tissue it "washes-out" chemicals that are not inside or bound to cells. The solution is collected after leaving the tissue and is analyzed to determine its components. A drug, such as an SSRI, can be added to the solution so that the tissue is exposed to the drug. In order to determine if a drug blocks serotonin reuptake it is applied to a tissue and the amount of serotonin that is present in the collected material is determined. In the case of a drug that blocks serotonin reuptake, the amount of serotonin that is present in the extracellular space will be increased, so more serotonin is available to be "washed out" of the tissue and, therefore, will be collected from the tissue. In order to determine if the drug selectively blocks serotonin reuptake, the solution is also analyzed for other neurotransmitters, such as norepinephrine. Here are references to a couple of recent scientific studes that employed microdialysis. 1 Dawson, L.A., & Nguyen, H.Q. (2000) The role of 5-HT(1A) and 5-HT(1B/1D) receptors on the modulation of acute fluoxetine-induced changes in extracellular 5-HT: the mechanism of action of (+/-)pindolol. Neuropharmacology, Vol. 39, pp. 1044-52 2 Cui, M., Feng, Y., McAdoo, D.J., & Willis, W.D. (1999) Periaqueductal Gray Stimulation-Induced Inhibition of Nociceptive Dorsal Horn Neurons in Rats Is Associated with the Release of Norepinephrine, Serotonin, and Amino Acids. The Journal of Pharmacology and Experimental Therapeutics, Vol. 289, pp. 868-876,
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