Neurobehavioral teratogenic effects of clomipramine and alpha-methyldopa

Boer, Sander; Mirmiran, M.; Haaren, Frans van; Louwerse, Annet L.; Poll, Nanne E. van de

doi:10.1016/0892-0362(89)90089-5

Cited by 12 publications

(6 citation statements)

References 23 publications

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“…Moreover, the serum drug/metabolite concentrations achieved in the neonatal rats are quite similar to those achieved in humans at therapeutic doses of these drugs. It is noteworthy that throughout the adult life, only clomipramine-exposed animals had a lower body weight than saline-treated which is consistent with previous studies (Corner et al, 1980;De Boer et al, 1989), whereas there was no difference in body Lasting neonatal SSRI effects on 5HT circuits D Maciag et al weight between saline-and citalopram-exposed rats. Thus citalopram-exposed rats with no symptoms of malnutrition or abnormal physical signs exhibited abnormalities in adult behavior typical of NADES.…”

Section: Discussionsupporting

confidence: 89%

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Maciąg

Simpson

Coppinger

et al. 2005

Neuropsychopharmacol

274

275

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A significant fraction of infants born to mothers taking selective serotonin reuptake inhibitors (SSRIs) during late pregnancy display clear signs of antidepressant withdrawal indicating that these drugs can penetrate fetal brain in utero at biologically significant levels. Previous studies in rodents have demonstrated that early exposure to some antidepressants can result in persistent abnormalities in adult behavior and indices of monoaminergic activity. Here, we show that chronic neonatal (postnatal days 8-21) exposure to citalopram (5 mg/kg, twice daily, s.c.), a potent and highly selective SSRI, results in profound reductions in both the rate-limiting serotonin synthetic enzyme (tryptophan hydroxylase) in dorsal raphe and in serotonin transporter expression in cortex that persist into adulthood. Furthermore, neonatal exposure to citalopram produces selective changes in behavior in adult rats including increased locomotor activity and decreased sexual behavior similar to that previously reported for antidepressants that are nonselective monoamine transport inhibitors. These data indicate that the previously reported neurobehavioral effects of antidepressants are a consequence of their effects on the serotonin transporter. Moreover, these data argue that exposure to SSRIs at an early age can disrupt the normal maturation of the serotonin system and alter serotonin-dependent neuronal processes. It is not known whether this effect of SSRIs is paralleled in humans; however, these data suggest that in utero, exposure to SSRIs may have unforeseen long-term neurobehavioral consequences.

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Section: Discussionsupporting

confidence: 89%

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Maciąg

Simpson

Coppinger

et al. 2005

Neuropsychopharmacol

274

275

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“…We have suppressed REM sleep during the 2nd and 3rd weeks of postnatal development in rats using an antidepressant drug such as clomipramine or an antihypertensive drug clonidine. In adulthood, the neonatally REM sleep deprived animals showed increased anxiety, reduced sexual activity, and disturbed sleep [46,47,53,54]. Other investigators found similar results which included despair behavior, reduced pleasure seeking, and increased alcohol preference when using clomipramine or other antidepressants in rats [48, 55±58].…”

Section: Rem Sleep and Brain Developmentmentioning

confidence: 95%

Development of fetal and neonatal sleep and circadian rhythms

Mirmiran

Maas

Ariagno

2003

Sleep Medicine Reviews

Self Cite

339

273

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“…These and subsequent investigators reported a number of behavioral changes in these rats as adults including alterations in locomotor activity, anxiety-like behavior, increased immobility in forced swim test, reduced exploratory behaviors in open field testing, reduced male sexual activity and competence, increased ethanol consumption, dysregulation of the hypothalamic-pituitary-adrenal axis and alterations in REM sleep. (Mirmiran et al, 1981; De Boer et al, 1989; Maciag et al, 2006). Although some of the reported behavioral deficits have been difficult to replicate across laboratories, impairment of male sexual behavior and disruption of aggressive behaviors have been remarkably consistent sequelae of early life antidepressant exposure (reviewed in (Vogel et al, 2000)).…”

Section: Introductionmentioning

confidence: 99%

Neonatal Exposure of Rats to Antidepressants Affects Behavioral Reactions to Novelty and Social Interactions in a Manner Analogous to Autistic Spectrum Disorders

Rodríguez‐Porcel

Green

Khatri

et al. 2011

The Anatomical Record

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We have demonstrated that neonatal exposure to selective serotonin reuptake inhibitors has lasting effects on behavior and serotonergic neurons in Long Evans rats. Hyperserotoninemia and altered sensory processing are reported in autistic spectrum disorders (ASD). We hypothesized that early life exposure to SSRIs alters sensory processing, disrupts responses to novelty and impairs social interactions in a manner similar to that observed in ASD. Male and female Long-Evans rat pups were administered citalopram, buproprion, fluoxetine, or saline from postnatal day (P) 8 to 21. Rats were tested for response to a novel tone before weaning (P25). Later, rats were tested 2× for response to a novel object (P39), and to a novel conspecific (P78, P101). In addition, rats were assessed for juvenile play behaviors (P32–P34) and later, we assessed sexual response to an estrus female in male rats (P153–184). Antidepressant exposure increased freezing after tone, diminished novel object exploration and reduced conspecific interaction up to 3× compared to saline exposed rats. Juvenile play was profoundly reduced in antidepressant-exposed males when compared to saline exposed groups. Exposure to the SSRIs, but not bupropion disrupted male sexual behaviors. Moreover, specific male responses to female proceptive behaviors were disrupted in SSRI, but not bupropion exposed rats. We conclude that neonatal exposure to antidepressants in rats results in sensory and social abnormalities that parallel many of those reported in ASD.

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Neurobehavioral teratogenic effects of clomipramine and alpha-methyldopa

Cited by 12 publications

References 23 publications

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Development of fetal and neonatal sleep and circadian rhythms

Neonatal Exposure of Rats to Antidepressants Affects Behavioral Reactions to Novelty and Social Interactions in a Manner Analogous to Autistic Spectrum Disorders

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