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Behavioral characterization of escalated aggression induced by GABA(B) receptor activation in the dorsal raphe nucleus.

ABSTRACT: Pharmacological activation of GABA(B) receptors in the dorsal raphe nucleus (DRN) can escalate territorial aggression in male mice.We characterized this escalated aggression in terms of its behavioral and environmental determinants.Aggressive behavior of resident male (CFW or ICR mouse) was assessed in confrontations with a group-housed intruder. Either baclofen (0.06 nmol/0.2 ?l) or vehicle (saline) was microinjected into the DRN 10 min before the confrontation. We examined baclofen-heightened aggression in five situations: aggression in a neutral arena and after social instigation (experiment 1), aggression during the light phase of the cycle (experiment 2), aggression without prior fighting experience (experiment 3), aggression toward a female (experiment 4), and aggression after defeat experiences (experiment 5). In addition, we examined the body targets towards which bites are directed and the duration of aggressive bursts after baclofen treatment.Regardless of the past social experience, baclofen escalated aggressive behaviors. Even in the neutral arena and after defeat experiences, where aggressive behaviors were inhibited, baclofen significantly increased aggression. Baclofen increased attack bites directed at vulnerable body areas of male intruders but not toward a female and only in the dark. Also, baclofen prolonged the duration of aggressive bursts.For baclofen to escalate aggression, specific stimulation (male intruder) and tonic level of serotonin (dark cycle) are required. Once aggressive behavior is triggered, intra-DRN baclofen escalates the level of aggression to abnormal levels and renders it difficult to terminate. Also, baclofen counteracts the effects of novelty or past experiences of defeat.

SUBMITTER: Takahashi A

PROVIDER: S-EPMC3694325 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Behavioral characterization of escalated aggression induced by GABA(B) receptor activation in the dorsal raphe nucleus.

Takahashi Aki A Schilit Arielle N AN Kim Jisoo J Debold Joseph F JF Koide Tsuyoshi T Miczek Klaus A KA

Psychopharmacology 20120307 1

<h4>Rationale</h4>Pharmacological activation of GABA(B) receptors in the dorsal raphe nucleus (DRN) can escalate territorial aggression in male mice.<h4>Objectives</h4>We characterized this escalated aggression in terms of its behavioral and environmental determinants.<h4>Methods</h4>Aggressive behavior of resident male (CFW or ICR mouse) was assessed in confrontations with a group-housed intruder. Either baclofen (0.06 nmol/0.2 μl) or vehicle (saline) was microinjected into the DRN 10 min befor ...[more]

PMID: 22395428

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Project description:Previous neuroimaging studies have suggested that the experience of flow aligns with a relative increase in activation of the dorsal raphe nucleus (DRN), and relative activation decreases of the medial prefrontal cortex (MPFC) and of the amygdala (AMY). In the present study, Dynamic Causal Modeling (DCM) was used to explore effective connectivity between those brain regions. To test our hypothesis that the DRN causally down-regulates activity of the MPFC and/or of the AMY, 23 healthy male students solved mental arithmetic tasks of varying difficulty during functional magnetic resonance imaging. A "flow" condition, with task demands automatically balanced with participants' skill level, was compared with conditions of "boredom" and "overload". DCM models were constructed modeling full reciprocal endogenous connections between the DRN, the MPFC, the AMY, and the calcarine. The calcarine was included to allow sensory input to enter the system. Experimental conditions were modeled as exerting modulatory effects on various possible connections between the DRN, the MPFC, and the AMY, but not on self-inhibitory connections, yielding a total of 64 alternative DCM models. Model space was partitioned into eight families based on commonalities in the arrangement of the modulatory effects. Random effects Bayesian Model Selection (BMS) was applied to identify a possible winning family (and model). Although BMS revealed a clear winning family, an outstanding winning model could not be identified. Therefore, Bayesian Model Averaging was performed over models within the winning family to obtain representative DCM parameters for subsequent analyses to test our hypothesis. In line with our expectations, Bayesian averaged parameters revealed stronger down-regulatory influence of the DRN on the MPFC when participants experienced flow relative to control conditions. In addition, these condition-dependent modulatory effects significantly predicted participants' experienced degree of flow. The AMY was down-regulated irrespective of condition. The present results suggest a causal role for the DRN in modulating the MPFC, contributing to the experience of flow.

Dataset Information

Behavioral characterization of escalated aggression induced by GABA(B) receptor activation in the dorsal raphe nucleus.

Publications

Behavioral characterization of escalated aggression induced by GABA(B) receptor activation in the dorsal raphe nucleus.

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