Down-regulation of 3H-imipramine binding sites in rat cerebral cortex after prenatal exposure to antidepressants.
Several antidepressant drugs were given to pregnant rats in the last 15 days of gestation and 3H-imipramine binding (3H-IMI) was subsequently measured in the cerebral cortex of the offspring. The selective serotonin (5-HT) uptake blockers chlorimipramine and fluoxetine as well as the selective monoamine oxidase (MAO) inhibitors clorgyline and deprenyl induced, after prenatal exposure, a down-regulation of 3H-IMI binding sites at postnatal day 25. The density of these binding sites was still reduced at postnatal day 90 in rats exposed in utero to the MAO inhibitors. The antidepressants desipramine and nomifensine were ineffective in this respect. After chronic treatment of adult animals, only chlorimipramine was able to down-regulate the 3H-IMI binding sites. Consequently, prenatal exposure of rats to different antidepressant drugs affecting predominantly the 5-HT systems induces more marked and long-lasting effects on cortical 3H-IMI binding sites. The results suggest that the developing brain is more susceptible to the actions of antidepressants.
Montero
D
D
Department of Neuropharmacology, Cajal Institute, C.S.I.C., Madrid, Spain.
de Ceballos
M L
ML
Del Rio
J
J
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000633:toxicity*; D001665:Binding Sites / Q000187:drug effects; D002352:Carrier Proteins; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D007099:Imipramine / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000633:toxicity
D000928:Antidepressive Agents; D002352:Carrier Proteins; D008996:Monoamine Oxidase Inhibitors; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter; D012702:Serotonin Antagonists; C027775:imipramine receptor; D007099:Imipramine