Individual differences in novelty-seeking predict differential responses to chronic antidepressant treatment through sex- and phenotype-dependent neurochemical signatures

Pitychoutis, Pothitos M.; Pallis, Eleftherios G.; Mikail, Hudu Garba; Papadopoulou-Daifoti, Z.

doi:10.1016/j.bbr.2011.04.036

Cited by 36 publications

(32 citation statements)

References 74 publications

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“…rodents (Nishitani et al, 2014), and recently, Gigliucci (Groenewegen and Uylings, 2000;Celada et al, 2004;592 Drevets, 2007;Anderson et al, 2011;Carballedo et al, 593 2011;Pitychoutis et al, 2011;Pitychoutis et al, 2012). (Silvestre et al, 1997).…”

Section: Q1mentioning

confidence: 96%

“…However, 85 whether this effect is restricted to certain brain regions 86 is not known. Notably, chronic treatment with conven- 87 tional antidepressants has been shown to affect the sero- 88 tonergic system and the levels of excitatory amino acids, 89 glutamate and aspartate, in the PFC and the hippocam-90 pus (HIPP) in a sex-dependent manner (Kokras et al, 91 2009;Pitychoutis et al, 2011Pitychoutis et al, , 2012 (Elizalde et al, 2008;Elizalde et al, 2010). After 2 weeks 247 of initial habituation to single housing, mice were trained 248 to consume a 2.5% sucrose solution every other night 249 (from 7:00 PM to 10:00 AM).…”

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confidence: 99%

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Sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naïve and “depressed” mice exposed to chronic mild stress

et al. 2015

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During the past decade, one of the most striking discoveries in the treatment of major depression was the clinical finding that a single infusion of a sub-anesthetic dose of the N-methyl-d-aspartate receptor antagonist ketamine produces a rapid (i.e. within a few hours) and long-lasting (i.e. up to two weeks) antidepressant effect in both treatment-resistant depressed patients and in animal models of depression. Notably, converging clinical and preclinical evidence support that responsiveness to antidepressant drugs is sex-differentiated. Strikingly, research regarding the antidepressant-like effects of ketamine has focused almost exclusively on the male sex. Herein we report that female C57BL/6J stress-naïve mice are more sensitive to the rapid and the sustained antidepressant-like effects of ketamine in the forced swim test (FST). In particular, female mice responded to lower doses of ketamine (i.e. 3mg/kg at 30 min and 5mg/kg at 24h post-injection), doses that were not effective in their male counterparts. Moreover, tissue levels of the excitatory amino acids glutamate and aspartate, as well as serotonergic activity, were affected in a sex-dependent manner in the prefrontal cortex and the hippocampus, at the same time-points. Most importantly, a single injection of ketamine (10mg/kg) induced sex-dependent behavioral effects in mice subjected to the chronic mild stress (CMS) model of depression. Intriguingly, female mice were more reactive to the earlier effects of ketamine, as assessed in the open field and the FST (at 30 min and 24h post-treatment, respectively) but the antidepressant potential of the drug proved to be longer lasting in males, as assessed in the splash test and the FST (days 5 and 7 post-treatment, respectively). Taken together, present data revealed that ketamine treatment induces sex-dependent rapid and sustained neurochemical and behavioral antidepressant-like effects in stress-naïve and CMS-exposed C57BL/6J mice.

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Section: Q1mentioning

confidence: 96%

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confidence: 99%

Sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naïve and “depressed” mice exposed to chronic mild stress

et al. 2015

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“…Most importantly, we recently reported that acute ketamine administration affects the levels of excitatory amino acid neurotransmitters (EAAs; glutamate and aspartate) and serotonergic activity in the HIPP and the PFC of stress-naïve mice in a sex-and brain region-dependent manner [18]. Indeed, both these brain regions have been strongly implicated in sex-related neurobehavioral responses to stress and antidepressant treatments [19][20][21][22][23][24][25].…”

Section: Research Highlightsmentioning

confidence: 99%

“…Since it is generally agreed that the first stage of any sex-difference study should be a comparison of gonadally intact adult females and males [34], a two-group design (males and females) was implemented for testing for sex-differentiated traits, as in previous studies from our laboratory [18,24,25]. …”

Section: Experimental Design and Drug Treatmentsmentioning

confidence: 99%

Repeated ketamine treatment induces sex-specific behavioral and neurochemical effects in mice

Thelen

Sens

Mauch

et al. 2016

Behavioural Brain Research

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“…DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and glutamate tissue concentrations in the PFC and the dSTR of Htr 2B +/+ and Htr 2B − / − mice were assessed ex vivo by means of high-performance liquid chromatography (HPLC) as previously described (Banas et al, 2011;Pitychoutis et al, 2011). A real-time qPCR-based approach was implemented to examine the mRNA expression of relevant key receptor genes pertaining to the dopaminergic and the glutamatergic neurochemical systems.…”

Section: Neurochemical Assessmentsmentioning

confidence: 99%

Mice Lacking the Serotonin Htr2B Receptor Gene Present an Antipsychotic-Sensitive Schizophrenic-Like Phenotype

Pitychoutis

Belmer

Moutkine

et al. 2015

Neuropsychopharmacol

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Impulsivity and hyperactivity share common ground with numerous mental disorders, including schizophrenia. Recently, a populationspecific serotonin 2B (5-HT 2B ) receptor stop codon (ie, HTR2B Q20*) was reported to segregate with severely impulsive individuals, whereas 5-HT 2B mutant (Htr 2B − / − ) mice also showed high impulsivity. Interestingly, in the same cohort, early-onset schizophrenia was more prevalent in HTR2B Q*20 carriers. However, the putative role of 5-HT 2B receptor in the neurobiology of schizophrenia has never been investigated. We assessed the effects of the genetic and the pharmacological ablation of 5-HT 2B receptors in mice subjected to a comprehensive series of behavioral test screenings for schizophrenic-like symptoms and investigated relevant dopaminergic and glutamatergic neurochemical alterations in the cortex and the striatum. Domains related to the positive, negative, and cognitive symptom clusters of schizophrenia were affected in Htr 2B − / − mice, as shown by deficits in sensorimotor gating, in selective attention, in social interactions, and in learning and memory processes. In addition, Htr 2B − / − mice presented with enhanced locomotor response to the psychostimulants dizocilpine and amphetamine, and with robust alterations in sleep architecture. Moreover, ablation of 5-HT 2B receptors induced a region-selective decrease of dopamine and glutamate concentrations in the dorsal striatum. Importantly, selected schizophreniclike phenotypes and endophenotypes were rescued by chronic haloperidol treatment. We report herein that 5-HT 2B receptor deficiency confers a wide spectrum of antipsychotic-sensitive schizophrenic-like behavioral and psychopharmacological phenotypes in mice and provide first evidence for a role of 5-HT 2B receptors in the neurobiology of psychotic disorders.

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Individual differences in novelty-seeking predict differential responses to chronic antidepressant treatment through sex- and phenotype-dependent neurochemical signatures

Cited by 36 publications

References 74 publications

Sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naïve and “depressed” mice exposed to chronic mild stress

Sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naïve and “depressed” mice exposed to chronic mild stress

Repeated ketamine treatment induces sex-specific behavioral and neurochemical effects in mice

Mice Lacking the Serotonin Htr2B Receptor Gene Present an Antipsychotic-Sensitive Schizophrenic-Like Phenotype

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