The serotonin 5-HT2A receptor subtype does not mediate apomorphine-induced aggressive behaviour in male Wistar rats

Skrebuhhova-Malmros, T.; Pruus, K.; Rudissaar, Ruth; Allikmets, Lembit; Matto, V.

doi:10.1016/s0091-3057(00)00368-3

Cited by 9 publications

(5 citation statements)

References 18 publications

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“…Evidence demonstrated that haloperidol did reduce the time spent in social interaction in male rat pairs using a social interaction paradigm [37, 49, 50] seems to be inconsistent to the present finding. An important property of haloperidol is to reduce aggressive behavior [51, 52], suggesting that an inhibition of increment in aggression by haloperidol injection results in a decreased time spent in social interaction in the social interaction paradigm. This, again, suggests a validation that the social investigation paradigm could dissociate the propensity to engage in social investigation from other related factors involving aggression, sexuality, and exploratory activity.…”

Section: Discussionmentioning

confidence: 99%

Validation of a novel social investigation task that may dissociate social motivation from exploratory activity

Deak

Arakawa

Bekkedal

et al. 2009

Behavioural Brain Research

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The present series of studies provide validation of a new paradigm that uniquely combines the assessment of the propensity to engage in social investigation with measures of (nonsocial) exploratory activity in rats. Assessment of this social investigation paradigm indicated that (a) rats showed a robust preference for social investigation over nonsocial exploratory activity, (b) female rats showed a greater preference for social investigation than male rats, (c) no signs of habituation in these responses were observed when rats were tested once daily for 4 consecutive days, (d) the preference for social investigation was stable and robust in both the dark and light periods of the daily light cycle for 5 consecutive days, and (e) testing under bright light conditions suppressed social investigation. In addition, acute administration of opiate drugs, low dose morphine (1.0 mg/kg) and naltrexone (1.0 mg/kg) produced a more robust attenuation of social investigation than nonsocial exploratory activity. Amphetamine increased both forms of investigation and haloperidol had the opposite effect, but the overall preference for social investigation over exploratory activity remained largely intact after both amphetamine and haloperidol injection. Together, these findings validate the use of this behavioral task to assess changes in social-motivation and general exploratory activity. Importantly, the task is bi-directionally sensitive to subject characteristics (i.e., sex), drug manipulations which modulate social motivation, and environmental manipulations.

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Section: Discussionmentioning

confidence: 99%

Validation of a novel social investigation task that may dissociate social motivation from exploratory activity

Deak

Arakawa

Bekkedal

et al. 2009

Behavioural Brain Research

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show abstract

“…Although both agonists and antagonists of 5-HT 2A receptors have been shown to reduce hostile behaviours (Olivier et al, 1995; Sakaue et al, 2002; White et al, 1991) [for contrasting results, see (Skrebuhhova-Malmros et al, 2000)], the interpretation of these findings is often complicated by the side effects of these compounds, such as the cognitive deficits induced by 5-HT 2A agonists and the sedative and hypolocomotive effects of their blockers (de Almeida et al, 2005). Little is currently known about the roles of different regions in the role of 5-HT 2A receptors in aggression; however, local infusion of 5-HT 2 agonists into the PAG was found to attenuate maternal aggression in rats (de Almeida et al, 2005).…”

Section: The Serotonergic System In Aggression and Suicidementioning

confidence: 99%

The role of the serotonergic system at the interface of aggression and suicide

et al. 2013

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Alterations in serotonin (5-HT) neurochemistry have been implicated in the aetiology of all major neuropsychiatric disorders, ranging from schizophrenia to mood and anxiety-spectrum disorders. This review will focus on the mulifaceted implications of 5-HT-ergic dysfunctions in the pathophysiology of aggressive and suicidal behaviours. After a brief overview of the anatomical distribution of the 5-HT-ergic system in the key brain areas that govern aggression and suicidal behaviours, the implication of 5-HT markers (5-HT receptors, transporter as well as synthetic and metabolic enzymes) in these conditions is discussed. In this regard, particular emphasis is placed on the integration of pharmacological and genetic evidence from animal studies with the findings of human experimental and genetic association studies. Traditional views postulated an inverse relationship between 5-HT and aggression and suicidal behaviours; however, ample evidence has shown that this perspective may be overly simplistic, and that such pathological manifestations may reflect alterations in 5-HT homeostasis due to the interaction of genetic, environmental and gender-related factors, particularly during early critical developmental stages. The development of animal models that may capture the complexity of such interactions promises to afford a powerful tool to elucidate the pathophysiology of impulsive aggression and suicidability, and find new effective therapies for these conditions.

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“…For instance, risperidone has been shown to attenuate aggression induced by social isolation in mice and apomorphine treatment in rats (Moechars et al 1998;Rodriguez-Arias et al 1998;Skrebuhhova-Malmros et al 2000). Moreover, our laboratory has previously demonstrated that acute and chronic risperidone treatment in a well-documented ethologically valid animal model of heightened offensive aggression reduced aggressive behaviors at doses comparable to those most effective in human adolescents Schwartzer et al 2008).…”

Section: Introductionmentioning

confidence: 95%

Paliperidone suppresses the development of the aggressive phenotype in a developmentally sensitive animal model of escalated aggression

et al. 2008

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Rationale Atypical antipsychotics are commonly prescribed to clinically referred youngsters for treatment of heightened aggressive behavior associated with various psychiatric disorders. Previously, we demonstrated risperidone's antiaggressive effects using a well-validated animal model of offensive aggression. Paliperidone, the main active metabolite of risperidone, is a potent serotonin-2A and dopamine-2 receptor antagonist with slightly different pharmacodynamic properties compared to risperidone. Given that much of risperidone's therapeutic efficacy is due to its active metabolite, paliperidone may effectively suppress aggression with fewer adverse side effects. Objectives Investigate whether paliperidone administration would reduce heightened aggressive behavior induced by low-dose cocaine exposure in a developmentally sensitive model of offensive aggression. Materials and methods Male Syrian hamsters (n=12/group) were administered an acute dose of paliperidone (0.05, 0.1, 0.2, and 0.3 mg/kg) and then tested for aggressive behavior using the resident-intruder paradigm. To investigate the effects of chronic paliperidone administration, a separate set of animals (n=12/group) was exposed to repeated paliperidone administration (0.1 mg kg −1 day −1 ) during different developmental periods and varying lengths of time (1-4 weeks). Results Experiment 1 results revealed a dose-dependent decrease in bite and attack behaviors with an effective dose observed at 0.1 mg/kg. In Experiment 2, the maximal reduction in aggressive behavior in response to chronic paliperidone treatment was observed in animals treated during the third week of adolescence, and this reduction occurred without concomitant alterations in non-aggressive behaviors.Conclusions These results support the specific aggressionsuppressing properties of paliperidone and the potential use of this compound in the treatment of maladaptive aggression in clinical settings.

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The serotonin 5-HT2A receptor subtype does not mediate apomorphine-induced aggressive behaviour in male Wistar rats

Cited by 9 publications

References 18 publications

Validation of a novel social investigation task that may dissociate social motivation from exploratory activity

Validation of a novel social investigation task that may dissociate social motivation from exploratory activity

The role of the serotonergic system at the interface of aggression and suicide

Paliperidone suppresses the development of the aggressive phenotype in a developmentally sensitive animal model of escalated aggression

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