title: Perinatal citalopram does not prevent the effect of prenatal stress on anxiety, depressive-like behaviour and serotonergic transmission in adult rat offspring.
abstract: It is still not clear whether the selective serotonin reuptake inhibitors frequently prescribed to depressed pregnant women improve the behavioural outcome in their children. The current study investigated whether administration of citalopram to pregnant rats could prevent anxiety and depressive-like behaviour induced by gestational stress in their offspring, and restore the expression of serotonin 1A autoreceptors in GABAergic interneurons in the medial prefrontal cortex and dorsal raphe nuclei in males, and of corticotropin-releasing factor type 2 receptors in GABAergic interneurons in the dorsal raphe nuclei in females. Activation of these receptors modulates serotonergic transmission to target areas and is reduced in a sex-dependent manner by prenatal stress. Citalopram (10 mg/kg/day), administered orally from day 7 of gestation until 21 days postpartum, prevented the increase in anxiety in stressed mothers but did not reduce anxiety and depressive-like behaviour in their offspring and even induced depressive-like behaviour in the offspring of control mothers. Citalopram failed to restore the reduction in the expression of serotonin 1A autoreceptors in the prefrontal cortex of males and in corticotropin-releasing factor type 2 receptors in the dorsal raphe nuclei of females induced by prenatal stress. Prenatal citalopram did not prevent the behavioural changes or reduction in serotonergic transmission to target areas induced by prenatal stress. It had adverse behavioural effects in the offspring of control rats, which, together with the lack of any change in prenatally-stressed rats, may be due to inhibition of the foetal serotonin transporter thereby preventing normal development of the serotonin system.
authors.affiliation: Department of Pharmacology, Institute of Drug Research, Hebrew University Medical Centre, Ein Kerem, Jerusalem, Israel.
authors.forename: Inbar
authors.initials: I
authors.lastname: Zohar
authors.affiliation: Department of Pharmacology, Institute of Drug Research, Hebrew University Medical Centre, Ein Kerem, Jerusalem, Israel.
authors.forename: Shai
authors.initials: S
authors.lastname: Shoham
authors.affiliation: Department of Pharmacology, Institute of Drug Research, Hebrew University Medical Centre, Ein Kerem, Jerusalem, Israel.
authors.forename: Marta
authors.initials: M
authors.lastname: Weinstock
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy*; D017660:Autoreceptors / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013312:Stress, Physiological
chemical_list: D017660:Autoreceptors; D015283:Citalopram; D003346:Corticotropin-Releasing Hormone; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
keywords: corticotropin-releasing factor type 2 receptors; dorsal raphe nuclei; medial prefrontal cortex; serotonin 1A autoreceptors; tryptophan hydroxylase