Neurokinin-1 expression and co-localization with glutamate and GABA in thehypothalamus of the cat

Recent behavioral studies using pharmacological techniques have demonstrate d that the high affinity substance P (SP) receptor, neurokinin-l receptor ( NK-1), in the medial hypothalamus could be important in mediating defensive rage behavior in the cat. These observations prompted us to use molecular techniques to determine the distribution of NK-1 in the hypothalamus and in other regions of the forebrain relevant to the control of rage behavior. W e cloned a 650 bp fragment of the cat NK-1 cDNA, Partial DNA sequence analy ses of this fragment indicate 90% homology with the human cDNA. By in situ hybridization (ISH), we showed that NK-1 mRNA was localized in the cytoplas m but not nuclei of cat forebrain neurons. Furthermore, NK-1 mRNA was co-lo calized in neurons that displayed positive immunolabeling for glutamate or GABA. Moderate labeling was visualized in the anterior medial hypothalamus which receives significant SP input via the stria terminalis from the media l amygdala. Strong labeling was also observed in the basal amygdaloid compl ex. The functional significance of this labeling pattern is suggested from the observation that both the medial and basal complex of amygdala serve as powerful modulators of defensive rage behavior. Weaker labeling was seen o ver the posterior medial and lateral hypothalamus, The distribution of NK-1 in the hypothalamus was matched by that of SP-immunoreactive axons and pre -terminals that were observed in the hypothalamus, The overall findings pro vide anatomical evidence to show that the high affinity SP receptor, NK-1, is linked to glutamate and GABA neurons in the anterior medial hypothalamus and further suggests its likely role in the regulation of feline aggressio n. (C) 1999 Elsevier Science B.V, All rights reserved.