Interleukin-1 beta in the hypothalamus potentiates feline defensive rage: role of serotonin-2 receptors.

The neurochemistry of aggression and rage has largely focused on the roles played by neurotransmitters and their receptor mechanisms. In contrast, little attention has been given to the possible functions of other substances. Interleukin-1beta is an immune and brain-derived cytokine that is present in the hypothalamus. Functionally, interleukin-1 has been shown to induce the release of serotonin (5-HT), a neurotransmitter known to potently affect aggression and rage behavior. Thus, the goal of the present study was to test the hypothesis that interleukin-1beta in the medial hypothalamus could modulate defensive rage behavior in the cat. In the first experiment, electrical stimulation of sites in the medial hypothalamus from which defensive rage could be elicited and where microinjections of specific compounds were later placed, facilitated defensive rage elicited from the periaqueductal gray (PAG), thus demonstrating the functional relationship between these two regions. In the second experiment, microinjections of relatively low doses of interleukin-1beta into the medial hypothalamus potentiated defensive rage behavior elicited from the midbrain periaqueductal gray in a dose-related manner. In the third experiment, pretreatment with a selective 5-HT2 receptor antagonist, LY-53857, blocked the facilitating effects of interleukin-1beta upon defensive rage. These findings reveal for the first time that brain cytokines can dramatically alter aggressive behavior. In particular, interleukin-1beta in the medial hypothalamus potentiates defensive rage behavior elicited from the periaqueductal gray in the cat, and the potentiating effects of interleukin-1beta on this form of emotional behavior are mediated via a 5-HT2 receptor mechanism.