NK1 receptors in the medial hypothalamus potentiate defensive rage behavior elicited from the midbrain periaqueductal gray of the cat.

Defensive rage in the cat occurs naturally in response to a threat and is also elicited by electrical or chemical stimulation over the rostro-caudal extent of the medial hypothalamus and dorsolateral aspect of the periaqueductal gray (PAG). This behavior is mediated over a descending projection from the hypothalamus to the midbrain PAG. The underlying hypothesis for the present study was that medial hypothalamic defensive rage neurons are excited in two ways: by NK(1) receptors and by an ascending input from the PAG. The first aspect of this hypothesis was tested by eliciting defensive rage by electrical stimulation of the PAG and then microinjecting a selective NK(1) agonist and antagonist into the hypothalamus. Microinjections of 16 or 12 nmol/0.25 microl of the NK(1) agonist, GR 73632, resulted in facilitation of defensive rage. These facilitatory effects were then blocked by pretreatment with the NK(1) antagonist, GR 82334. However, microinjections of GR 82334 alone had no effect. The second aspect of the hypothesis was tested by stimulating defensive rage sites in the PAG and using immunohistochemical methods to test for the presence of c-Fos in the hypothalamus. The results revealed the presence of c-Fos immunoreactivity in the medial but not lateral hypothalamus. Overall, the findings indicate that NK(1) receptors in the medial hypothalamus facilitate defensive rage elicited from PAG neurons whose axons project back to the medial hypothalamus. The likely ethological significance of the ascending input is that it allows for potentiation and prolongation of defensive rage in response to a threatening stimulus.