Cytokine modulation of defensive rage behavior in the cat: Role of GABAa and interleukin-2 receptors in the medial hypothalamus

Bhatt, Suresh; Zalcman, Steven S.; Hassanain, M.; Siegel, Allan

doi:10.1016/j.neuroscience.2005.01.065

Cited by 37 publications

(20 citation statements)

References 44 publications

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“…Small doses of Il-1b injected into the medial hypothalamus of cats increased defensive rage responses to an electrical stimulation in the brain which normally would produce a defensive rage response (Hassanain et al, 2003). In a similar model Il-2 suppresses the defensive rage responses (Bhatt et al, 2005). However peripheral administration of LPS suppressed defensive rage, and this effect was blocked by administering TNF-a receptor blockers (Bhatt et al, 2009).…”

Section: Irritability and Inflammationmentioning

confidence: 98%

A review of the neuro- and systemic inflammatory responses in post concussion symptoms: Introduction of the “post-inflammatory brain syndrome” PIBS

Rathbone

Tharmaradinam

Jiang

et al. 2015

Brain, Behavior, and Immunity

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Section: Irritability and Inflammationmentioning

confidence: 98%

A review of the neuro- and systemic inflammatory responses in post concussion symptoms: Introduction of the “post-inflammatory brain syndrome” PIBS

Rathbone

Tharmaradinam

Jiang

et al. 2015

Brain, Behavior, and Immunity

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“…Details of the surgical procedures have been described elsewhere Bhatt et al, 2005;Gregg and Siegel, 2003;Hassanain et al, 2003;Hassanain et al, 2005).…”

Section: Surgerymentioning

confidence: 99%

“…Defensive rage behavior was induced by utilizing procedures identical to those used previously in our laboratory Bhatt et al, 2005;Bhatt and Siegel, 2006;Hassanain et al, 2003;Hassanain et al, 2005;Jasper and Ajmone-Marsan, 1954). A cannula electrode (23 gauge) and a monopolar stimulating electrode (51.5 mm), both insulated throughout its length except at 0.5 mm from the tip (Plastics One, Roanoke, VA), were lowered into the PAG and medial hypothalamus, respectively.…”

Section: Elicitation Of Defensive Rage Behavior and Predatory Attackmentioning

confidence: 99%

Role of IL-1β and 5-HT2 receptors in midbrain periaqueductal gray (PAG) in potentiating defensive rage behavior in cat

Bhatt

Zalcman

et al. 2008

Brain, Behavior, and Immunity

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Feline defensive rage, a form of aggressive behavior that occurs in response to a threat can be elicited by electrical stimulation of the medial hypothalamus or midbrain periaqueductal gray (PAG). Our laboratory has recently begun a systematic examination of the role of cytokines in the regulation of rage and aggressive behavior. It was shown that the cytokine, interleukin-2 (IL-2), differentially modulates defensive rage when microinjected into the medial hypothalamus and PAG by acting through separate neurotransmitter systems. The present study sought to determine whether a similar relationship exists with respect to interleukin 1-β (IL-1β), whose receptor activation in the medial hypothalamus potentiates defensive rage. Thus, the present study identified the effects of administration of IL-1β into the PAG upon defensive rage elicited from the medial hypothalamus. Microinjections of IL-1β into the dorsal PAG significantly facilitated defensive rage behavior elicited from the medial hypothalamus in a dose and time dependent manner. In addition, the facilitative effects of IL-1β were blocked by pre-treatment with anti-IL-1β receptor antibody, while IL-1β administration into the PAG had no effect upon predatory attack elicited from the lateral hypothalamus. The findings further demonstrated that IL-1β's effects were mediated through 5-HT 2 receptors since pretreatment with a 5-HT 2C receptor antagonist blocked the facilitating effects of IL-1β. An extensive pattern of labeling of IL-1β and 5-HT 2C in the dorsal PAG supported these findings. The present study demonstrates that IL-1β in the dorsal PAG, similar to the medial hypothalamus, potentiates defensive rage behavior and is mediated through a 5-HT 2C receptor mechanism.

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“…In contrast, activation of IL-2 receptors in the same region of the medial hypothalamus suppresses defensive rage behavior. The suppressive effects of IL-2 are mediated through GABA A receptors [4]. Thus, these two cytokines utilize different neurotransmitter mechanisms within the medial hypothalamus to differentially modulate defensive rage behavior.…”

Section: Cytokines and Aggressionmentioning

confidence: 99%

The Neurobiological Bases for Development of Pharmacological Treatments of Aggressive Disorders

Siegel

Bhatt²,

Bhatt³

et al. 2007

123

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Violence and aggression are major causes of death and injury, thus constituting primary public health problems throughout much of the world costing billions of dollars to society. The present review relates our understanding of the neurobiology of aggression and rage to pharmacological treatment strategies that have been utilized and those which may be applied in the future. Knowledge of the neural mechanisms governing aggression and rage is derived from studies in cat and rodents. The primary brain structures involved in the expression of rage behavior include the hypothalamus and midbrain periaqueductal gray. Limbic structures, which include amygdala, hippocampal formation, septal area, prefrontal cortex and anterior cingulate gyrus serve important modulating functions. Excitatory neurotransmitters that potentiate rage behavior include excitatory amino acids, substance P, catecholamines, cholecystokinin, vasopressin, and serotonin that act through 5-HT2 receptors. Inhibitory neurotransmitters include GABA, enkephalins, and serotonin that act through 5-HT1 receptors. Recent studies have demonstrated that brain cytokines, including IL-1 and IL-2, powerfully modulate rage behavior. IL-1 exerts its actions by acting through 5-HT2 receptors, while IL-2 acts through GABAA or NK1 receptors. Pharmacological treatment strategies utilized for control of violent behavior have met with varying degrees of success. The most common approach has been to apply serotonergic compounds. Others included the application of antipsychotic, GABAergic (anti-epileptic) and dopaminergic drugs. Present and futures studies on the neurobiology of aggression may provide the basis for new and novel treatment strategies for the control of aggression and violence as well as the continuation of existing pharmacological approaches.

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Cytokine modulation of defensive rage behavior in the cat: Role of GABAa and interleukin-2 receptors in the medial hypothalamus

Cited by 37 publications

References 44 publications

A review of the neuro- and systemic inflammatory responses in post concussion symptoms: Introduction of the “post-inflammatory brain syndrome” PIBS

A review of the neuro- and systemic inflammatory responses in post concussion symptoms: Introduction of the “post-inflammatory brain syndrome” PIBS

Role of IL-1β and 5-HT2 receptors in midbrain periaqueductal gray (PAG) in potentiating defensive rage behavior in cat

The Neurobiological Bases for Development of Pharmacological Treatments of Aggressive Disorders

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