Role of IL-1 beta and 5-HT2 receptors in midbrain periaqueductal gray (PAG) in potentiating defensive rage behavior in cat.
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-beta (IL-1 beta), whose receptor activation in the medial hypothalamus potentiates defensive rage. Thus, the present study identified the effects of administration of IL-1 beta into the PAG upon defensive rage elicited from the medial hypothalamus. Microinjections of IL-1 beta 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-1 beta were blocked by pre-treatment with anti-IL-1 beta receptor antibody, while IL-1 beta administration into the PAG had no effect upon predatory attack elicited from the lateral hypothalamus. The findings further demonstrated that IL-1 beta's effects were mediated through 5-HT(2) receptors since pretreatment with a 5-HT(2C) receptors antagonist blocked the facilitating effects of IL-1 beta. An extensive pattern of labeling of IL-1 beta and 5-HT(2C) receptors in the dorsal PAG supported these findings. The present study demonstrates that IL-beta in the dorsal PAG, similar to the medial hypothalamus, potentiates defensive rage behavior and is mediated through a 5-HT(2C) receptor mechanism.
Bhatt
Suresh
S
Department of Neurology & Neurosciences, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA.
Bhatt
Rekha
R
Zalcman
Steven S
SS
Siegel
Allan
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001522:Behavior, Animal / Q000502:physiology; D002415:Cats; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D007026:Hypothalamic Area, Lateral / Q000502:physiology; D007033:Hypothalamus, Middle / Q000502:physiology; D053583:Interleukin-1beta / Q000494:pharmacology / Q000502:physiology*; D008845:Microinjections; D015213:Neuroimmunomodulation / Q000502:physiology*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D011235:Predatory Behavior / Q000502:physiology; D011889:Rage / Q000502:physiology*; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000276:immunology / Q000378:metabolism; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology
D000906:Antibodies; D004873:Ergolines; D053583:Interleukin-1beta; D043887:Receptor, Cholecystokinin B; D044405:Receptor, Serotonin, 5-HT2C; D017472:Receptors, Interleukin-1; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D015320:Tachykinins; C032663:LY 53857