title: Antidepressants influence somatostatin levels and receptor pharmacology in brain.
abstract: This study investigated how the administration (acute and chronic) of the antidepressants citalopram and desmethylimipramine (DMI) influences somatostatin (somatotropin release inhibitory factor, SRIF) levels and SRIF receptor density (sst(1-5)) in rat brain. Animals received either of the following treatments: (1) saline for 21 days (control group), (2) saline for 20 days and citalopram or DMI for 1 day (citalopram or DMI acute groups), (3) citalopram or DMI for 21 days (citalopram or DMI chronic groups). Somatostatin levels were determined by radioimmunoassay. [(125)I]LTT SRIF-28 binding in the absence (labeling of sst(1-5)) or presence of 3 nM MK678 (labeling of sst(1/4)) and [(125)I]Tyr(3) octreotide (labeling of sst(2/5)) binding with subsequent autoradiography was performed in brains of rats treated with both antidepressants. Somatostatin levels were increased after citalopram, but not DMI administration, in the caudate-putamen, hippocampus, nucleus accumbens, and prefrontal cortex. Autoradiography studies illustrated a significant decrease in receptor density in the superficial and deep layers of frontal cortex (sst(2)), as well as a significant increase in the CA1 (sst(1/4)) hippocampal field in brains of chronically citalopram-treated animals. DMI administration increased sst(1/4) receptors levels in the CA1 hippocampal region. These results suggest that citalopram and to a lesser extent DMI influence the function of the somatostatin system in brain regions involved in the emotional, motivational, and cognitive aspects of behavior.
authors.affiliation: Department of Basic Sciences, Laboratory of Pharmacology, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Pallis
authors.forename: Anna
authors.initials: A
authors.lastname: Vasilaki
authors.forename: Dominique
authors.initials: D
authors.lastname: Fehlmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Kastellakis
authors.forename: Daniel
authors.initials: D
authors.lastname: Hoyer
authors.forename: Christina
authors.initials: C
authors.lastname: Spyraki
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Thermos
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D015283:Citalopram / Q000008:administration & dosage*; D003891:Desipramine / Q000008:administration & dosage*; D007118:Immunoassay; D007457:Iodine Radioisotopes; D008297:Male; D015282:Octreotide; D010456:Peptides, Cyclic; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D007457:Iodine Radioisotopes; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; D015283:Citalopram; D013004:Somatostatin; C040968:seglitide; D015282:Octreotide; D003891:Desipramine