Involvement of benzodiazepine binding sites in an antiaggressive effect by 5-HT1A receptor activation in isolated mice

Sakaue, Masaki; Ago, Yukio; Murakami, Chika; Sowa, Chikako; Sakamoto, Yasuhisa; Kōyama, Yutaka; Baba, Akemichi; Matsuda, Takehisa

doi:10.1016/s0014-2999(01)01511-4

Cited by 38 publications

(31 citation statements)

References 12 publications

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“…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: 99%

“…LY379268 (1 mg/kg) or saline was also given as a single-dose injection 60 min before the encounter (Figures 5-8). These doses of the drugs used here were determined by referring to previous studies: the doses potently inhibited isolation rearing-induced aggressive behavior, hyperactivity, deficits of prepulse inhibition, or cognitive impairments (Jones et al, 2011;Sakaue et al, 2001Sakaue et al, , 2003.…”

Section: Animals and Drugsmentioning

confidence: 99%

“…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%

“…Diazepam is a potent anxiolytic (do-Rego et al, 2006) and attenuates aggressive behavior (Sakaue et al, 2001;Wongwitdecha and Marsden, 1996) and anxiety-like behavior in the elevated plus-maze (Da Silva et al, 1996) in isolation-reared rodents. Osemozotan and mGlu 2/3 receptor agonists also inhibit aggressive behavior and anxiety-like behavior in the elevated plus-maze, and they reverse the deficits of prepulse Figure 8 Effects of diazepam and osemozotan (a), and LY379268 (b) on encounter-induced increases in extracellular 5-HT levels in the nucleus accumbens shell of male isolation-reared mice.…”

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

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: Animals and Drugsmentioning

confidence: 99%

Section: Animals and Drugsmentioning

confidence: 99%

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

confidence: 99%

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

confidence: 99%

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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Selective antiaggressive effect of an alpha‐2 adrenoceptor agonist naphthylmedetomidine in mice

Votava

Hess

Kršiak

2008

Aggressive Behavior

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Alpha-2 adrenoceptors (alpha(2)-ARs) are critically involved in regulating neurotransmitter release from sympathetic nerves and neurons and play an important role in the regulation of awareness, arousal and vigilance. In our recent study, dexmedetomidine, a full alpha(2)-AR agonist, produced antiaggressive effects in the social conflict test in mice at doses that were twice smaller than those producing sedation. The aim of this study was to ascertain antiaggressive effect of a novel drug naphthylmedetomidine, with a more selective alpha(2)-AR activity. Behavioral effects of naphthylmedetomidine (150-1200 microg/kg i.p.) were studied in the activity cage and in the social conflict tests in mice. Naphthylmedetomidine dose dependently decreased aggressive behavior during social conflict in aggressive mice with significant reduction already at the lowest doses tested (150 microg/kg), whereas locomotion and social investigation were significantly decreased only after four times bigger dose of naphthylmedetomidine (600 microg/kg) in aggressive mice. Naphthylmedetomidine had no effect on aggression in nonaggressive mice. Naphthylmedetomidine reduced locomotion in the activity cage significantly only at the highest doses tested (600 and 1200 microg/kg), and this effect was only partially reversed by administration of high doses of an alpha-2 antagonist atipamezole (3 and 10 mg/kg). In nonaggressive mice, the difference between the dose reducing dominant social behavior (social investigation) and locomotion (150 and 300 microg/kg, respectively) was smaller than in aggressive mice. In conclusion, naphthylmedetomidine showed a very strong and selective antiaggressive effect in aggressive mice, which was devoid of locomotion-inhibiting/sedative effect. This study suggests that naphthylmedetomidine may have clinical potential as antiaggressive drug.

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Modification of cocaine-induced behavioral and neurochemical effects by serotonin1A receptor agonist/antagonist in mice

Nakamura

Ago

Hayashi

et al. 2006

Synapse

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Administration of cocaine causes a locomotor stimulant effect and increases extracellular levels of serotonin (5-HT) and dopamine (DA) in the brains of rodents. Previous studies show that 5-HT1A receptor agonist and antagonist modify the cocaine-induced behavioral and neurochemical effects in the rats. However, the role of the 5-HT system on the effects of cocaine has not been studied in the prefrontal cortex. The present study examined in ddY-strain male mice the effects of the 5-HT1A receptor agonist osemozotan and the receptor antagonist WAY100635 on cocaine-induced locomotor stimulant effect and increases in extracellular levels of 5-HT and DA in the prefrontal cortex. The cocaine-induced locomotor stimulant effect was attenuated by osemozotan and enhanced by WAY100635. The cocaine-induced increase in extracellular levels of 5-HT was attenuated by osemozotan, and enhanced by WAY100635. The cocaine-induced increase in extracellular levels of DA was enhanced by osemozotan, but not affected by WAY100635. These results suggest that the prefrontal 5-HT system plays a pivotal role in the locomotor stimulant effect of cocaine in mice.

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Involvement of benzodiazepine binding sites in an antiaggressive effect by 5-HT1A receptor activation in isolated mice

Cited by 38 publications

References 12 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

Selective antiaggressive effect of an alpha‐2 adrenoceptor agonist naphthylmedetomidine in mice

Modification of cocaine-induced behavioral and neurochemical effects by serotonin1A receptor agonist/antagonist in mice

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