Effect of repeated administration of antidepressants on serotonin uptake sites in limbic and neocortical structures of rat brain determined by quantitative autoradiography.
The binding of 3H-cyanoimipramine, a selective radioligand for the serotonin (5-HT) transporter, was measured by quantitative autoradiography on sections of rat brain to determine if 5-HT uptake sites are regulated by repeated administration of antidepressants. The drugs studied included selective inhibitors of the uptake of 5-HT (citalopram, sertraline) or norepinephrine (protriptyline). Also, effects of inhibitors of monoamine oxidase (MAO) that inhibit both type A and type B MAO (phenelzine), or just type B MAO (deprenyl), were investigated. In addition, the atypical antidepressant mianserin, which has antagonist properties at both alpha 2 adrenoceptors and 5-HT2 receptors, was studied. A total of 19 limbic areas and 4 regions of the parietal cortex were quantitated. The binding of 3H-cyanoimipramine was increased (14% to 31%) by phenelzine and deprenyl in a total of 3 brain areas and decreased (15% to 21%) by sertraline in 4 brain areas. Citalopram, protriptyline, and mianserin produced no statistically significant effect in any brain region examined. The results indicate that different types of antidepressants do not exert consistent or substantial regulatory effect on the density of uptake sites for 5-HT in the limbic system or parietal cortex.
Kovachich
G B
GB
Department of Veterans Affairs Medical Center, University of Pennsylvania School of Medicine, Philadelphia.
Aronson
C E
CE
Brunswick
D J
DJ
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001345:Autoradiography; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D007099:Imipramine / Q000031:analogs & derivatives / Q000494:pharmacology; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D000928:Antidepressive Agents; D007099:Imipramine; D008996:Monoamine Oxidase Inhibitors; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C024316:cianopramine