Potentiating role of interleukin-1beta (IL-1beta) and IL-1beta type 1 receptors in the medial hypothalamus in defensive rage behavior in the cat.
Recently, this laboratory provided evidence that interleukin-1beta (IL-1beta), an immune and brain-derived cytokine, microinjected into the medial hypothalamus, potentiates defensive rage behavior in the cat elicited from the midbrain periaqueductal gray (PAG), and that such effects are blocked by a 5-HT2 receptor antagonist. Since this finding represents the first time that a brain cytokine has been shown to affect defensive rage behavior, the present study replicated and extended these findings by documenting the specific potentiating role played by IL-1beta Type 1 receptor (IL-1RI), and the anatomical relationship between IL-1beta and 5-HT2 receptors in the medial hypothalamus. IL-1beta (10 ng) microinjected into the medial hypothalamus induced two separate phases of facilitation, one at 60 min and another at 180 min, post-injection. In turn, these effects were blocked with pretreatment of the selective IL-1 Type I receptor antagonist (IL-1ra) (10 ng), demonstrating the selectivity of the effects of IL-1beta on medial hypothalamic neurons upon PAG-elicited defensive rage behavior. The next stage of the study utilized immunohistochemical methods to demonstrate that IL-1beta and 5-HT2 receptors were present on the same neurons within regions of the medial hypothalamus where IL-1beta and the IL-1beta receptor antagonists were administered. This provided anatomical evidence suggesting a relationship between IL-1RI and 5-HT2 receptors in the medial hypothalamus that is consistent with the previous pharmacological observations in our laboratory. The overall findings show that activation of IL-1RI in the medial hypothalamus potentiates defensive rage behavior in the cat and that these effects may also be linked to the presence of 5-HT2 receptors on the same groups of neurons in this region of hypothalamus.
Hassanain
M
M
Department of Neurology and Neuroscience, UMDNJ-New Jersey Medical School, MSB Room H-512, 185 South Orange Avenue, Newark, NJ 07103, USA.
Bhatt
S
S
Zalcman
S
S
Siegel
A
A
D000374:Aggression / Q000502:physiology* / Q000528:radiation effects; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D006801:Humans; D007033:Hypothalamus, Middle / Q000502:physiology* / Q000528:radiation effects; D007150:Immunohistochemistry / Q000379:methods; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000528:radiation effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D053573:Receptors, Interleukin-1 Type I; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology; D013997:Time Factors
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016760:Proto-Oncogene Proteins c-fos; D044405:Receptor, Serotonin, 5-HT2C; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D011994:Recombinant Proteins; D012795:Sialoglycoproteins