Antidepressants influence somatostatin levels and receptor pharmacology in brain.
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.
Pallis
Eleftherios
E
Department of Basic Sciences, Laboratory of Pharmacology, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
Vasilaki
Anna
A
Fehlmann
Dominique
D
Kastellakis
Andreas
A
Hoyer
Daniel
D
Spyraki
Christina
C
Thermos
Kyriaki
K
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*
D000928:Antidepressive Agents; D007457:Iodine Radioisotopes; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; D015283:Citalopram; D013004:Somatostatin; C040968:seglitide; D015282:Octreotide; D003891:Desipramine