ABSTRACT
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.
Subject(s)
Aggression/physiology , Hypothalamus, Middle/physiology , Interleukin-1/metabolism , Receptors, Interleukin-1/metabolism , Aggression/radiation effects , Analysis of Variance , Animals , Behavior, Animal , Cats , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Drug Interactions , Electric Stimulation/methods , Female , Humans , Hypothalamus, Middle/radiation effects , Immunohistochemistry/methods , Interleukin 1 Receptor Antagonist Protein , Interleukin-1/pharmacology , Periaqueductal Gray/radiation effects , Proto-Oncogene Proteins c-fos/metabolism , Reaction Time/drug effects , Receptor, Serotonin, 5-HT2C/metabolism , Receptors, Interleukin-1 Type I , Recombinant Proteins/pharmacology , Sialoglycoproteins/pharmacology , Time FactorsABSTRACT
A significant increase of cell multiplication in inoculated ascitic and solid tumors was demonstrated in both DBA/2 and C57BL/6 mice as well as in Wistar rats after radiofrequency lesions in the median hypothalamus (ventromedial and dorsomedial nuclei; part of arcuate nucleus). The following tests were performed: mitotic and metaphasic index, doubling time of tumor, incorporation of tritiated thymidine into DNA, cell cycle parameters and growth fraction. The increased rate of cell proliferation measured was predominantly due to the higher speed of DNA biosynthesis with a minor contribution by an increase of the growth fraction. In the animals with hypothalamic lesions we demonstrated a slight decrease in the secretory activity of the adenohypophysis. Because it is generally stated that failure of hypophysis function hinders cell multiplication in normal and neoplastic tissues, we think that heightened cell proliferation after hypothalamic lesions is due to suppression of an inhibitory mechanism located in the hypothalamus and which is independent of the hypophysis.
Subject(s)
Hypothalamus, Middle/physiology , Neoplasms, Experimental/pathology , Animals , Cell Division , Growth Hormone/blood , Hypothalamus, Middle/radiation effects , Leukemia L1210/pathology , Lung Neoplasms/pathology , Male , Mice , Mice, Inbred Strains , Neoplasms, Experimental/blood , Radio Waves , Rats , Rats, Inbred Strains , Sarcoma, Yoshida/pathologyABSTRACT
En experimentos efectuados en conejos se estudiaron las manifestaciones emotivo-conductuales surgidas de la estimulación del hipotálamo medial. La estimulación eléctrica de los núcleos dorsomediales, ventromediales y posteriores del hipotálamo, provocó una conducta de evitación en el fondo de la acción de la corriente, y una conducta de golpeo con las extremidades posteriores sobre el piso, específico de la especie, en el período post-estimulador. Se estudió en el período de lactancia (PL), aparición del primer golpeo seguido al cese de la estimulación, la cantidad total de golpeo y particularmente la dinámica del desarrollo de la reacción en dependencia de la duración de la estimulación (T), en el período comprendido desde el primer segundo, hasta los 20 segundos. Se estableció asimismo que la cantidad de golpeos crece regularmente a medida que aumenta T desde 1 segundo hasta 10 segundos y luego comienza a disminuir(AU)
