Long-lasting behavioural and molecular alterations induced by early postnatal fluoxetine exposure are restored by chronic fluoxetine treatment in adult mice

Karpova, Nina N.; Lindholm, Jesse; Pruunsild, Priit; Timmusk, Tõnis; Ċastrén, Eero

doi:10.1016/j.euroneuro.2008.09.002

Cited by 132 publications

(163 citation statements)

References 75 publications

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“…Neonatal administration of ADs (such as clomipramine, citalopram, or fluoxetine) to rodents during the early life period (from PN8 to PN21) was shown to produce a constellation of maladaptive behaviors, possibly related to anxiety and depression, that persist in adulthood (Vogel et al, 1988;Andersen et al, 2002;Ansorge et al, 2004;Maciag et al, 2006;Popa et al, 2008). In this study, postnatal exposure to the SSRI fluoxetine significantly decreased visits to an openfield center in adulthood while increasing total immobility time in the FST, in agreement with previous reports (Ansorge et al, 2004;Karpova et al, 2009;Popa et al, 2010). 5-HT 1A receptors have been proposed to have a crucial role in the mediation of such a deleterious action of SERT blockade (Alexandre et al, 2006;Popa et al, 2008) In contrast, such behavioral disturbances were not observed after a neonatal administration of AS19 or SB-269970.…”

Section: Discussionsupporting

confidence: 81%

Pharmacological Blockade of 5-HT7 Receptors as a Putative Fast Acting Antidepressant Strategy

Mnie-Filali

Faure

Lambás‐Señas

et al. 2011

Neuropsychopharmacol

128

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Current antidepressants still display unsatisfactory efficacy and a delayed onset of therapeutic action. Here we show that the pharmacological blockade of serotonin 7 (5-HT 7 ) receptors produced a faster antidepressant-like response than the commonly prescribed antidepressant fluoxetine. In the rat, the selective 5-HT 7 receptor antagonist SB-269970 counteracted the anxiogenic-like effect of fluoxetine in the open field and exerted an antidepressant-like effect in the forced swim test. In vivo, 5-HT 7 receptors negatively regulate the firing activity of dorsal raphe 5-HT neurons and become desensitized after long-term administration of fluoxetine. In contrast with fluoxetine, a 1-week treatment with SB-269970 did not alter 5-HT firing activity but desensitized cell body 5-HT autoreceptors, enhanced the hippocampal cell proliferation, and counteracted the depressive-like behavior in olfactory bulbectomized rats. Finally, unlike fluoxetine, early-life administration of SB-269970, did not induce anxious/depressive-like behaviors in adulthood. Together, these findings indicate that the 5-HT 7 receptor antagonists may represent a new class of antidepressants with faster therapeutic action.

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Section: Discussionsupporting

confidence: 81%

Pharmacological Blockade of 5-HT7 Receptors as a Putative Fast Acting Antidepressant Strategy

Mnie-Filali

Faure

Lambás‐Señas

et al. 2011

Neuropsychopharmacol

128

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“…2E)-a measure of behavioral despair in rodents used to screen for antidepressants (51,52). These findings replicate previous results of early-life FLX treatment (48,53) and are comparable with those obtained after infant trauma, as modeled by paired odor-shock conditioning (Fig. 3C) (12) or rearing with an abusive mother (13,19).…”

Section: Infant Trauma Induces Preference Learning Of Trauma Cues Andsupporting

confidence: 81%

“…2D) associated with later-life depressive-like behavior ( Fig. 3 A and C), providing insight into possible mechanisms by which early-life FLX treatment produces detrimental effects (46,48,53,58). These data demonstrate that 5-HT is developmentally sensitive to infant experiences and that alterations in 5-HT during critical periods in early life can be a predisposing factor for later-life affective dysfunction (41-43, 47, 57).…”

Section: Discussionmentioning

confidence: 96%

Enduring good memories of infant trauma: Rescue of adult neurobehavioral deficits via amygdala serotonin and corticosterone interaction

Rincón-Cortés

Barr

Mouly

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Children form a strong attachment to their caregiver-even when that caretaker is abusive. Paradoxically, despite the trauma experienced within this relationship, the child develops a preference for trauma-linked cues-a phenomenon known as trauma bonding. Although infant trauma compromises neurobehavioral development, the mechanisms underlying the interaction between infant trauma bonding (i.e., learned preference for trauma cues) and the long-term effects of trauma (i.e., depressive-like behavior, amygdala dysfunction) are unknown. We modeled infant trauma bonding by using odor-shock conditioning in rat pups, which engages the attachment system and produces a life-long preference for the odor that was paired with shock. In adulthood, this trauma-linked odor rescues depressive-like behavior and amygdala dysfunction, reduces corticosterone (CORT) levels, and exerts repair-related changes at the molecular level. Amygdala microarray after rescue implicates serotonin (5-HT) and glucocorticoids (GCs), and a causal role was verified through microinfusions. Blocking amygdala 5-HT eliminates the rescue effect; increasing amygdala 5-HT and blocking systemic CORT mimics it. Our findings suggest that infant trauma cues share properties with antidepressants and safety signals and provide insight into mechanisms by which infant trauma memories remain powerful throughout life.E arly-life trauma is associated with compromised neurobehavioral development and vulnerability to later-life psychiatric disorders like depression (1-5). Long-lasting effects of infant trauma relevant to depression include disruptions in social behavior, alterations in the serotonin (5-HT) system, and amygdala dysfunction (2, 5-8), which have been replicated by animal models (9-15). Paradoxically, trauma-linked cues-even those associated with abusive attachment-can elicit strong attraction and feelings of comfort in humans (16,17). Furthermore, a lifelong attraction to trauma-linked cues has also been demonstrated in rodent models of infant trauma, which suggests that sensory cues learned during infancy alter adult behaviors and amygdala activity (12,18,19).To explore the enduring effects of infant trauma and the mechanisms underlying their modulation by infant trauma-linked cues, we used an odor-learning paradigm during the sensitive period for attachment learning in rat pups, postnatal (PN) days 8-12, which is characterized by rapid and robust odor-preference learning that extends to aversive stimuli (14,(20)(21)(22). Specifically, we used infant olfactory classical conditioning in which a novel peppermint odor is paired with a mild shock (0.5 mA, 1s) to produce a preferred odor that functions behaviorally as a maternal odor and results in neural activation comparable with that induced by natural maternal odor (20,(23)(24)(25). During the sensitive period, low endogenous levels of corticosterone (CORT) and attenuated shock-induced CORT release prevent the infant amygdala from exhibiting the learning-induced plasticity required for avoidance learning (1...

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“…It is curious to note that a single immobilization stress, which induces a transient decrease in BDNF mRNA levels in the hippocampus, also induced a transient decrease in H3 acetylation that returns to baseline by 24 h (Fuchikami et al, 2009). A study examining the induction of BDNF after chronic postnatal fluoxetine exposure in normal mice did not find corresponding changes in H3 acetylation or methylation changes, and points to the necessity for preexisting stress states for epigenetic changes associated with antidepressant treatment (Karpova et al, 2009).…”

Section: Identification Of Gene Targets: Genome-wide and Promoter-spementioning

confidence: 99%

Epigenetics of the Depressed Brain: Role of Histone Acetylation and Methylation

Sun

Kennedy

Nestler

2012

Neuropsychopharmacol

342

233

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Major depressive disorder is a chronic, remitting syndrome involving widely distributed circuits in the brain. Stable alterations in gene expression that contribute to structural and functional changes in multiple brain regions are implicated in the heterogeneity and pathogenesis of the illness. Epigenetic events that alter chromatin structure to regulate programs of gene expression have been associated with depression-related behavior, antidepressant action, and resistance to depression or 'resilience' in animal models, with increasing evidence for similar mechanisms occurring in postmortem brains of depressed humans. In this review, we discuss recent advances in our understanding of epigenetic contributions to depression, in particular the role of histone acetylation and methylation, which are revealing novel mechanistic insight into the syndrome that may aid in the development of novel targets for depression treatment.

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Long-lasting behavioural and molecular alterations induced by early postnatal fluoxetine exposure are restored by chronic fluoxetine treatment in adult mice

Cited by 132 publications

References 75 publications

Pharmacological Blockade of 5-HT7 Receptors as a Putative Fast Acting Antidepressant Strategy

Pharmacological Blockade of 5-HT7 Receptors as a Putative Fast Acting Antidepressant Strategy

Enduring good memories of infant trauma: Rescue of adult neurobehavioral deficits via amygdala serotonin and corticosterone interaction

Epigenetics of the Depressed Brain: Role of Histone Acetylation and Methylation

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