Cytokine modulation of defensive rage behavior in the cat: role of GABAA and interleukin-2 receptors in the medial hypothalamus.
Defensive rage behavior is a form of aggressive behavior occurring in nature in response to a threatening stimulus. It is also elicited by stimulation of the medial hypothalamus and midbrain periaqueductal gray (PAG) and mediated through specific neurotransmitter-receptor mechanisms within these regions. Since interleukin (IL)-2 modulates the release of neurotransmitters linked to aggression and rage, we sought to determine whether IL-2 microinjected into the medial hypothalamus would modulate defensive rage. Microinjections of relatively low doses of IL-2 into the medial hypothalamus significantly suppressed defensive rage elicited from the PAG in a dose-dependent manner and in the absence of signs of sickness behavior. Pre-treatment with an antibody directed against IL-2Ralpha or a GABA(A) receptor antagonist blocked IL-2's suppressive effects upon defensive rage. Since the suppression of defensive rage is also mediated by 5-HT(1) receptors in the medial hypothalamus, a 5-HT(1) antagonist was microinjected into this region as a pretreatment for IL-2; however, it did not block IL-2's suppressive effects. Immunocytochemical data provided anatomical support for these findings by revealing extensive labeling of IL-2Ralpha on neurons in the medial hypothalamus. IL-2 microinjected into the medial hypothalamus did not modulate predatory attack elicited from the lateral hypothalamus. In summary, we provide evidence for a novel role for IL-2 in the medial hypothalamus as a potent suppressor of defensive rage behavior. These effects are mediated through an IL-2-GABA(A) receptor mechanism.
Bhatt
S
S
Department of Neurology and Neurosciences, New Jersey Medical School, Medical Science Building, Room H-512, 185 South Orange Avenue, Newark, NJ 07103, USA.
Zalcman
S
S
Hassanain
M
M
Siegel
A
A
D000374:Aggression / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D019138:Antibodies, Blocking; D001640:Bicuculline / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D002415:Cats; D016207:Cytokines / Q000502:physiology*; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000494:pharmacology; D008845:Microinjections; D011235:Predatory Behavior / Q000187:drug effects; D011889:Rage / Q000187:drug effects / Q000502:physiology*; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D019138:Antibodies, Blocking; D016207:Cytokines; D018756:GABA Antagonists; D007376:Interleukin-2; D011963:Receptors, GABA-A; D015375:Receptors, Interleukin-2; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D001640:Bicuculline