Serotonin 5-HT(2C) receptor-mediated phosphoinositide hydrolysis in rat choroid plexus after fluoxetine and citalopram treatments. Export

@article{citeulike:117712, abstract = {Selective serotonin reuptake inhibitors (SSRIs) bind directly to various neurotransmitter receptors. The clinical effects of SSRIs appear gradually during weeks of treatment, suggesting a role for adaptive changes in neurotransmitter receptors. Most clinically used antidepressants, e.g. fluoxetine, bind to 5-HT(2C) receptors. When administered chronically, many antidepressants elicit adaptive regulation of 5-HT(2C) receptors. The present study was conducted in order to determine the effects of acute and chronic fluoxetine and citalopram treatments on the density and function of 5-HT(2C) receptors in the rat choroid plexus. Acute and chronic treatments followed by phosphoinositide (PI) hydrolysis assays and quantitative receptor autoradiography were performed. Acute (single-dose) treatment with neither drug significantly affected basal or 5-HT-stimulated PI hydrolysis, but acute citalopram (20mg/kg) treatment increased both agonist and antagonist binding to 5-HT(2C) receptors. Chronic (14 days) citalopram treatment (20mg/kg) increased the maximal PI hydrolysis response by 40\%, but fluoxetine lacked this effect. The present data suggest that sensitisation of 5-HT(2C) receptor-mediated intracellular signal transduction may play a role in the effects of citalopram. In contrast, fluoxetine treatment does not functionally sensitise 5-HT(2C) receptors. Thus, functional 5-HT(2C) receptor sensitisation is not a common effect of antidepressants, but the differential effects may explain some of the pharmacodynamic differences seen with these drugs, especially upon repeated administration.}, address = {Department of Neurosurgery, Helsinki University Central Hospital, 00029 HUS, Finland.}, author = {P\"{a}lvim\"{a}ki, E. P. and Majasuo, H. and Syv\"{a}lahti, E. and Hietala, J.}, citeulike-article-id = {117712}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.phrs.2004.11.005}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15749456}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15749456}, doi = {10.1016/j.phrs.2004.11.005}, issn = {1043-6618}, journal = {Pharmacol Res}, keywords = {citalopram, fluoxetine}, month = {May}, number = {5}, pages = {419--425}, posted-at = {2005-03-09 08:04:16}, priority = {2}, title = {Serotonin 5-HT(2C) receptor-mediated phosphoinositide hydrolysis in rat choroid plexus after fluoxetine and citalopram treatments.}, url = {http://dx.doi.org/10.1016/j.phrs.2004.11.005}, volume = {51}, year = {2005} }

TY - JOUR ID - citeulike:117712 L3 - citeulike-article-id:117712 N2 - Selective serotonin reuptake inhibitors (SSRIs) bind directly to various neurotransmitter receptors. The clinical effects of SSRIs appear gradually during weeks of treatment, suggesting a role for adaptive changes in neurotransmitter receptors. Most clinically used antidepressants, e.g. fluoxetine, bind to 5-HT(2C) receptors. When administered chronically, many antidepressants elicit adaptive regulation of 5-HT(2C) receptors. The present study was conducted in order to determine the effects of acute and chronic fluoxetine and citalopram treatments on the density and function of 5-HT(2C) receptors in the rat choroid plexus. Acute and chronic treatments followed by phosphoinositide (PI) hydrolysis assays and quantitative receptor autoradiography were performed. Acute (single-dose) treatment with neither drug significantly affected basal or 5-HT-stimulated PI hydrolysis, but acute citalopram (20mg/kg) treatment increased both agonist and antagonist binding to 5-HT(2C) receptors. Chronic (14 days) citalopram treatment (20mg/kg) increased the maximal PI hydrolysis response by 40%, but fluoxetine lacked this effect. The present data suggest that sensitisation of 5-HT(2C) receptor-mediated intracellular signal transduction may play a role in the effects of citalopram. In contrast, fluoxetine treatment does not functionally sensitise 5-HT(2C) receptors. Thus, functional 5-HT(2C) receptor sensitisation is not a common effect of antidepressants, but the differential effects may explain some of the pharmacodynamic differences seen with these drugs, especially upon repeated administration. IS - 5 JF - Pharmacol Res SN - 1043-6618 AD - Department of Neurosurgery, Helsinki University Central Hospital, 00029 HUS, Finland. EP - 425 TI - Serotonin 5-HT(2C) receptor-mediated phosphoinositide hydrolysis in rat choroid plexus after fluoxetine and citalopram treatments. VL - 51 SP - 419 KW - citalopram KW - fluoxetine AU - Pälvimäki, EP AU - Majasuo, H AU - Syvälahti, E AU - Hietala, J PY - 2005/05// UR - http://dx.doi.org/10.1016/j.phrs.2004.11.005 ER -