Decreased anxiety-like behavior and locomotor/exploratory activity, and modulation in hypothalamus, hippocampus, and frontal cortex redox profile in sexually receptive female rats after short-term exposure to male chemical cues

Behr, Guilherme Antônio; Motta, Leonardo Lisbôa da; Oliveira, Marcos Roberto de; Oliveira, Max William Soares; Hoff, Mariana Leivas Müller; Silvestrin, Roberta Bristot; Moreira, José Cláudio Fonseca

doi:10.1016/j.bbr.2008.11.047

Cited by 10 publications

(5 citation statements)

References 66 publications

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“…This suggests that the structural and functional abnormalities induced by PAK inactivation in the frontal cortex of 3xTg-AD mice are involved in AD-associated social changes and support idea that the 3xTg-AD-dnPAK mouse is a model of advanced AD. In addition, the higher level of anxiety observed in 3xTg-AD-dnPAK mice is in agreement with the most important morphometric abnormalities observed in frontal cortex, a cerebral structure involved in the circuitry of anxiety [92, 93]. In conclusion, the role of PAK on neuronal morphology and on the fronto-dependent behavioral alterations in AD conditions demonstrated the potential of this protein as a therapeutic target in the treatment of AD-related psychiatric symptoms.…”

Section: Discussionsupporting

confidence: 81%

Transgenic autoinhibition of p21-activated kinase exacerbates synaptic impairments and fronto-dependent behavioral deficits in an animal model of Alzheimer’s disease

Bories

Arsenault

Lemire

et al. 2017

Aging

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Defects in p21-activated kinase (PAK) lead to dendritic spine abnormalities and are sufficient to cause cognition impairment. The decrease in PAK in the brain of Alzheimer's disease (AD) patients is suspected to underlie synaptic and dendritic disturbances associated with its clinical expression, particularly with symptoms related to frontal cortex dysfunction. To investigate the role of PAK combined with Aβ and tau pathologies (3xTg-AD mice) in the frontal cortex, we generated a transgenic model of AD with a deficit in PAK activity (3xTg-AD-dnPAK mice). PAK inactivation had no effect on Aβ40 and Aβ42 levels, but increased the phosphorylation ratio of tau in detergent-insoluble protein fractions in the frontal cortex of 18-month-old heterozygous 3xTg-AD mice. Morphometric analyses of layer II/III pyramidal neurons in the frontal cortex showed that 3xTg-AD-dnPAK neurons exhibited significant dendritic attrition, lower spine density and longer spines compared to NonTg and 3xTg-AD mice. Finally, behavioral assessments revealed that 3xTg-AD-dnPAK mice exhibited pronounced anxious traits and disturbances in social behaviors, reminiscent of fronto-dependent symptoms observed in AD. Our results substantiate a critical role for PAK in the genesis of neuronal abnormalities in the frontal cortex underlying the emergence of psychiatric-like symptoms in AD.

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Section: Discussionsupporting

confidence: 81%

Transgenic autoinhibition of p21-activated kinase exacerbates synaptic impairments and fronto-dependent behavioral deficits in an animal model of Alzheimer’s disease

Bories

Arsenault

Lemire

et al. 2017

Aging

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“…Of particular interest is ER-α which is expressed more during non-estrus phases [73] and could therefore be responsible for increased NMDA receptor function and greater ketamine efficacy. It is also possible that the oxidative profile of free radical oxygen species generation/clearance is highly dynamic and region-specific in the female brain [74, 75].…”

Section: Discussionmentioning

confidence: 99%

NMDA 2A receptors in parvalbumin cells mediate sex-specific rapid ketamine response on cortical activity

et al. 2019

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Ketamine has emerged as a widespread treatment for a variety of psychiatric disorders when used at sub-anesthetic doses, but the neural mechanisms underlying its acute action remain unclear. Here, we identified NMDA receptors containing the 2A subunit (GluN2A) on parvalbumin (PV)-expressing inhibitory interneurons as a pivotal target of low-dose ketamine. Genetically deleting GluN2A receptors globally or selectively from PV interneurons abolished the rapid enhancement of visual cortical responses and gamma-band oscillations by ketamine. Moreover, during the follicular phase of the estrous cycle in female mice, the ketamine response was transiently attenuated along with a concomitant decrease of grin2A mRNA expression within PV interneurons. Thus, GluN2A receptors on PV interneurons mediate the immediate actions of low-dose ketamine treatment, and fluctuations in receptor expression across the estrous cycle may underlie sex-differences in drug efficacy.

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“…While the elevated plus maze and light-dark box exploration test typically provide consistent results, [27, 28] such congruent findings are not universal. For instance, exposure to male chemical cues is anxiolytic in sexually receptive females when measured on the elevated plus maze, but the same cues modestly increase anxiety in the light-dark box exploration test [40]. In addition, phencyclidine (PCP) induces anxiety in young adult rats when assessed on the elevated plus maze, but PCP decreases anxiety in the light-dark box test [39].…”

Section: Discussionmentioning

confidence: 99%

Novelty-induced conditioned place preference, sucrose preference, and elevated plus maze behavior in adult rats after repeated exposure to methylphenidate during the preweanling period

Crawford

Der-Ghazarian

Britt

et al. 2013

Behavioural Brain Research

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Early treatment with methylphenidate has a persistent effect on the affective (i.e., anxiety- and depressive-like) behaviors of adult rats and mice. Interestingly, age at methylphenidate exposure appears to be a critical determinant influencing the expression of affective behaviors. In the present study, we exposed rats to methylphenidate during the preweanling period (i.e., PD 11-PD 20) because this ontogenetic period is analogous to early childhood in humans (an age associated with increasing methylphenidate usage). Rats were injected with methylphenidate (0, 2, or 5 mg/kg) from PD 11 to PD 20 and reactivity to rewarding and aversive stimuli were measured in early adulthood. Specifically, novelty-induced CPP, sucrose preference, and elevated plus maze behavior were assessed on PD 60. Early treatment with 2 or 5 mg/kg methylphenidate increased total time spent in the white compartment of the CPP chamber. This methylphenidate-induced effect occurred regardless of exposure condition. Performance on the elevated plus maze was also impacted by early methylphenidate exposure, because rats treated with 5 mg/kg methylphenidate spent more time in the closed compartment of the elevated plus maze than vehicle controls. Early methylphenidate exposure did not alter sucrose preference. These data indicate that exposing rats to methylphenidate during the preweanling period differentially affects anxiety-like behavior depending on the type of anxiety-provoking stimulus. Specifically, early methylphenidate exposure decreased aversion to a bright white room when measured on a novelty-induced CPP task, whereas methylphenidate caused a long-term increase in anxiety when measured on the elevated plus maze.

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Decreased anxiety-like behavior and locomotor/exploratory activity, and modulation in hypothalamus, hippocampus, and frontal cortex redox profile in sexually receptive female rats after short-term exposure to male chemical cues

Cited by 10 publications

References 66 publications

Transgenic autoinhibition of p21-activated kinase exacerbates synaptic impairments and fronto-dependent behavioral deficits in an animal model of Alzheimer’s disease

Transgenic autoinhibition of p21-activated kinase exacerbates synaptic impairments and fronto-dependent behavioral deficits in an animal model of Alzheimer’s disease

NMDA 2A receptors in parvalbumin cells mediate sex-specific rapid ketamine response on cortical activity

Novelty-induced conditioned place preference, sucrose preference, and elevated plus maze behavior in adult rats after repeated exposure to methylphenidate during the preweanling period

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