The Selective Metabotropic Glutamate 2/3 Receptor Agonist MGS0028 Reverses Isolation Rearing–Induced Abnormal Behaviors in Mice

Ago, Yukio; Araki, Ryoko; Yano, Koji; Kawasaki, Toshiyuki; Chaki, Shigeyuki; Nakazato, Atsuro; Onoe, Hirotaka; Hashimoto, Hitoshi; Baba, Akemichi; Takuma, Kazuhiro; Matsuda, Takehisa

doi:10.1254/jphs.11200sc

Cited by 31 publications

(25 citation statements)

References 15 publications

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“…The data are expressed as the mean ± SEM of 10 mice/group. inhibition in isolation-reared animals (Ago et al, 2012;Maisonnette et al, 1993;Sakaue et al, 2001Sakaue et al, , 2003Sánchez et al, 1993). The present study demonstrated that encounter-induced hyperactivity and increased prefrontal 5-HT levels were blocked by diazepam, osemozotan, and LY379268.…”

Section: Effect Of Encounter Stimulation In Isolated Mice Y Ago Et Alsupporting

confidence: 56%

“…However, the mice were able to see, hear, and smell their neighbor. Thus, a social encounter with an unfamiliar conspecific through a mesh partition is considered a form of psychological stress, and it is useful for studies of the neurochemical changes that may be involved in the abnormal behaviors of isolation-reared animals (Ago et al, 2012;Fone and Porkess, 2008;Lukkes et al, 2009a, b;Pinna et al, 2008). In this study, the total time that the resident mice spent near the partition and the total time the resident and intruder mice spent interacting did not differ between the male group-reared, female isolation-reared, and male isolation-reared mice (Figure 1c).…”

Section: Discussionmentioning

confidence: 99%

“…All experiments were conducted on 9-week-old male or female mice. The isolated male ddY-strain mice showed abnormal behaviors (Ago et al, 2007(Ago et al, , 2012Sakaue et al, 2001Sakaue et al, , 2003 consistent with those in C57BL/6J or ICR strain mice (Ibi et (Tocris Cookson, Bristol, UK), and pentobarbital (Nacalai Tesque, Kyoto, Japan) were used in this study. Osemozotan and diazepam were suspended in 0.5% w/v carboxymethylcellulose.…”

Section: Animals and Drugsmentioning

confidence: 98%

“…Previous studies have shown that gamma-aminobutyric acid A (GABA A ) receptor agonists, 5-HT 1A receptor agonists, and mGlu 2/3 receptor agonists attenuate isolation-rearinginduced aggressive behaviors and/or anxiety-like behaviors (Ago et al, 2012;Da Silva et al, 1996;Maisonnette et al, 1993;Sakaue et al, 2001;Sánchez et al, 1993;Wongwitdecha and Marsden, 1996). Thus, we next examined the effects of the GABA A receptor agonist diazepam, the 5-HT 1A receptor agonist osemozotan, and the mGlu 2/3 receptor agonist LY379268 on encounter-induced behavioral changes in male isolation-reared mice ( Figure 5).…”

Section: Effects Of Diazepam Osemozotan and Ly379268 On Encounter-imentioning

confidence: 99%

“…Post-weaning social isolation is a useful model to study the effects of adverse early-life experiences on behavior and the neural mechanisms associated with isolation-induced changes in mood and anxiety (Lapiz et al, 2003;Lukkes et al, 2009c). Previous pharmacological studies have shown that serotonin 1A (5-HT 1A ) receptor agonists and metabotropic glutamate 2/3 (mGlu 2/3 ) receptor agonists reverse isolation-rearing-induced abnormal behaviors (Ago et al, 2012;Jones et al, 2011;Maisonnette et al, 1993;Sakaue et al, 2001Sakaue et al, , 2003Sánchez et al, 1993), but the exact neurochemical mechanisms are not known. There have been several studies on the neurochemical effects of isolation rearing, particularly focusing on the monoaminergic systems.…”

Section: Introductionmentioning

confidence: 99%

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Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Ago

Araki

Tanaka

et al. 2013

Neuropsychopharmacol

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Isolation-reared male rodents show abnormal behaviors such as hyperlocomotion, aggressive behaviors, deficits of prepulse inhibition, and depression-and anxiety-like behaviors, but the neurochemical mechanism for the effects of psychological stress in these animals is not fully understood. This study examined the effects of social interactions between isolation-reared mice and intruder mice on brain monoaminergic systems. A cage was divided into two compartments by a mesh partition to prevent direct physical interactions. The 20-min encounter with an intruder elicited a restless and hyperexcitable state (hyperactivity) in male, but not in female, isolationreared mice, whereas encounters with a sleeping intruder or a novel object did not. Although the encounter did not affect prefrontal neuronal-activity-marker c-Fos expression, dopamine (DA) levels, or serotonin (5-HT) levels in male group-reared mice or female isolation-reared mice, it increased prefrontal c-Fos expression, DA levels, and 5-HT levels in male isolation-reared mice. Furthermore, encounter-induced increases in c-Fos expression in the dorsal raphe nucleus and ventral tegmental area, but not in the nucleus accumbens shell, were much greater in isolation-reared than group-reared male mice. A 5-HT 1A receptor agonist, a metabotropic glutamate 2/3 receptor agonist, and a gamma-aminobutyric acid A receptor agonist attenuated isolation-induced aggressive behaviors and encounter-induced hyperactivity, c-Fos expression in the prefrontal cortex and dorsal raphe nucleus, and increases in prefrontal 5-HT levels. These findings suggest that the prefrontal DA and 5-HT systems are activated by encounter stimulation in male isolationreared mice, and the encounter-induced activation of 5-HT system triggers the induction of some abnormal behaviors in male isolation-reared mice. Furthermore, this study implies that the encounter stimulation-induced signal has a pharmacological significance.

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Section: Effect Of Encounter Stimulation In Isolated Mice Y Ago Et Alsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Animals and Drugsmentioning

confidence: 98%

Section: Effects Of Diazepam Osemozotan and Ly379268 On Encounter-imentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

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Araki

Tanaka

et al. 2013

Neuropsychopharmacol

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The Role of Neurotransmitters in Violence and Aggression

Miczek

DeBold

Gobrogge

et al. 2017

The Wiley Handbook of Violence and Aggression

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Like all behaviors, aggression and violence have their roots in neurobiology. In this chapter, we review research that explores the roles of serotonin, norepinephrine, dopamine, glutamate, and γ‐aminobutyric acid (GABA) in aggressive behavior. We highlight how maladaptive aggression is determined by neural activity in specific pathways and receptors in the serotonin system, which in turn are modulated by catecholamines, GABA, and glutamate. In addition, these neurotransmitter systems are modulated by several neuropeptides, prominently by vasopressin, oxytocin, corticotropin‐releasing factor, and the endogenous opioid peptides. These modulatory systems of serotonergic microcircuits form networks with several nodes for diagnostic measures and therapeutic intervention in veterinary and human medicine.

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The neurobiological basis of human aggression: A review on genetic and epigenetic mechanisms

Waltes

Chiocchetti

Freitag

2015

American J of Med Genetics Pt B

146

105

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Aggression is an evolutionary conserved behavior present in most species including humans. Inadequate aggression can lead to long-term detrimental personal and societal effects. Here, we differentiate between proactive and reactive forms of aggression and review the genetic determinants of it. Heritability estimates of aggression in general vary between studies due to differing assessment instruments for aggressive behavior (AB) as well as age and gender of study participants. In addition, especially non-shared environmental factors shape AB. Current hypotheses suggest that environmental effects such as early life stress or chronic psychosocial risk factors (e.g., maltreatment) and variation in genes related to neuroendocrine, dopaminergic as well as serotonergic systems increase the risk to develop AB. In this review, we summarize the current knowledge of the genetics of human aggression based on twin studies, genetic association studies, animal models, and epigenetic analyses with the aim to differentiate between mechanisms associated with proactive or reactive aggression. We hypothesize that from a genetic perspective, the aminergic systems are likely to regulate both reactive and proactive aggression, whereas the endocrine pathways seem to be more involved in regulation of reactive aggression through modulation of impulsivity. Epigenetic studies on aggression have associated non-genetic risk factors with modifications of the stress response and the immune system. Finally, we point to the urgent need for further genome-wide analyses and the integration of genetic and epigenetic information to understand individual differences in reactive and proactive AB.

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The Selective Metabotropic Glutamate 2/3 Receptor Agonist MGS0028 Reverses Isolation Rearing–Induced Abnormal Behaviors in Mice

Cited by 31 publications

References 15 publications

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

The Role of Neurotransmitters in Violence and Aggression

The neurobiological basis of human aggression: A review on genetic and epigenetic mechanisms

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