Increased adult behavioral ‘despair’ in rats neonatally exposed to desipramine or zimeldine: An animal model of depression?

Hilakivi, Leena A.; Hilakivi, I.

doi:10.1016/0091-3057(87)90454-0

Cited by 81 publications

(31 citation statements)

References 13 publications

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“…In neonatal rodents, chronic administration of serotonin reuptake inhibitors (clomipramine, fluoxetine, zimeldine, LU-10-134C) as well as some other tricyclic antidepressants but not the atypical antidepressants iprindole or nomifensine during the early life period from postnatal day 8 (PN8) to PN21 results in a pattern of maladaptive behaviors that are evident long after drug discontinuation and persist into adulthood (Mirmiran et al, 1981;Hilakivi et al, 1984;Hilakivi and Hilakivi, 1987;Hansen et al, 1997;Ansorge et al, 2004). These behavioral changes, described here as the 'neonatal antidepressant exposure syndrome (NADES)', in rats include alterations in locomotor activity, reduced male sexual activity and competence, increased ethanol consumption, dysregulation of the hypothalamic-pituitaryadrenal axis, increased rapid eye movement (REM) sleep time and reduced latency to enter the REM sleep phase, and increased immobility in the forced swim test (Mirmiran et al, 1981;Hilakivi et al, 1984;Hilakivi and Hilakivi, 1987;Hartley et al, 1990;Hansen et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…These behavioral changes, described here as the 'neonatal antidepressant exposure syndrome (NADES)', in rats include alterations in locomotor activity, reduced male sexual activity and competence, increased ethanol consumption, dysregulation of the hypothalamic-pituitaryadrenal axis, increased rapid eye movement (REM) sleep time and reduced latency to enter the REM sleep phase, and increased immobility in the forced swim test (Mirmiran et al, 1981;Hilakivi et al, 1984;Hilakivi and Hilakivi, 1987;Hartley et al, 1990;Hansen et al, 1997). In contrast, adults exposed to similar doses and durations of antidepressants exhibit no persistent behavioral effects after drug discontinuation, indicating that the neurobiological response to long-term antidepressant administration differs markedly between early life and adulthood.…”

Section: Introductionmentioning

confidence: 99%

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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: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Maciąg

Simpson

Coppinger

et al. 2005

Neuropsychopharmacol

274

275

View full text Add to dashboard Cite

show abstract

“…A number of observations support this hypothesis. First, treating non-mutant rats and mice with SERT-blocking SRIs such as fluoxetine during the first weeks of life (corresponding to late pregnancy in humans) mimics the increased anxiety-and depression-like phenotype of Slc6a4 knockout (Andersen et al, 2002;Ansorge et al, 2004Ansorge et al, , 2008Feng et al, 2001b;Hilakivi and Hilakivi, 1987;Maciag et al, 2006aMaciag et al, , 2006b). Second, Alexandre and colleagues have shown that either depleting serotonin levels with PCPA or inhibiting 5-HT1A-Rs with WAY 100635 during the first few weeks of life, both of which presumably block some of the actions of excessive neonatal serotonin, is sufficient to rescue some of the depression-related abnormalities in adult SERT knockout mice (Alexandre et al, 2006).…”

Section: Serotonin Reuptakementioning

confidence: 99%

Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease

Holmes

2008

Neuroscience & Biobehavioral Reviews

249

166

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The serotonin system is strongly implicated in the pathophysiology and therapeutic alleviation of stress-related disorders such as anxiety and depression. Serotonergic modulation of the acute response to stress and the adaptation to chronic stress is mediated by a myriad of molecules controlling serotonin neuron development (Pet-1), synthesis (tryptophan hydroxylase 1 and 2 isozymes), packaging (vesicular monoamine transporter 2), actions at presynaptic and postsynaptic receptors (5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, 5-HT3A, 5-HT4, 5-HT5A, 5-HT6, 5-HT7), reuptake (serotonin transporter), and degradation (monoamine oxidase A). A growing body of evidence from preclinical rodents models, and especially genetically modified mice and inbred mouse strains, has provided significant insight into how genetic variation in these molecules can affect the development and function of a key neural circuit between the dorsal raphe nucleus, medial prefrontal cortex and amygdala. By extension, such variation is hypothesized to have a major influence on individual differences in the stress response and risk for stress-related disease in humans. The current article provides an update on this rapidly evolving field of research.

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“…In addition, rats deprived of REM sleep, using both an instrumental model 113 or a pharmacological model, develop multiple adverse behavioral changes, [113][114][115][116][117][118][119] as well as a significant decrease in the cerebral cortex and brainstem volume. 115,116 Neurotransmitters.…”

Section: Role Of Sleep In Brain Developmentmentioning

confidence: 99%

“…281 Selective serotonin re-uptake inhibitor medications (desipramine, zimeldine, clomipramine) have been used to achieve an animal model for REM sleep deprivation. 114,119 Narcotics and sedatives including morphine, phenobarbital and diazepam alters the preterm newborn EEG tracing with a depressive effect. 282,283 Awareness of the potential negative impact of these pharmacologic therapies on neonatal sleep and brain development, should be part of a considered decision to utilize pharmacologic therapies to relieve pain and stress.…”

Section: To 32 Weeks Gestational Age and Beyondmentioning

confidence: 99%

The development of potentially better practices to support the neurodevelopment of infants in the NICU

et al. 2007

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Objective: To review the existing evidence used to identify potentially better care practices that support newborn brain development.Study Design: Literature review.Result: Sixteen potentially better practices are identified and grouped into two operational clinical bundles based upon timing for recommended implementation. Conclusion:Existing evidence supports the implementation of selected care practices that potentially may support newborn brain development.

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Increased adult behavioral ‘despair’ in rats neonatally exposed to desipramine or zimeldine: An animal model of depression?

Cited by 81 publications

References 13 publications

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease

The development of potentially better practices to support the neurodevelopment of infants in the NICU

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