NEUROTENSIN INDUCES FOS AND ZIF268 EXPRESSION IN LIMBIC NUCLEI OF THERAT-BRAIN

The endogenous tridecapeptide neurotensin exerts a wide range of behav ioral, electrophysiological and neurochemical effects when administere d directly into the brain. These effects are thought to result from th e activation of distinct populations of neurotensin receptors distribu ted throughout the central nervous system. We have mapped the sites of functional change in the rat brain associated with the central admini stration of neurotensin using the induction of the nuclear protein pro ducts of the immediate early genes c-fos and zif268 as markers of cell ular activation. The administration of neurotensin into the lateral ve ntricle of rats produced an increase in the number of nuclei positive for Fos and Zif268 immunoreactivity in the central and basolateral nuc lei of the amygdala and the paraventricular and supraoptic nuclei of t he hypothalamus. Neurotensin also produced an increase in serum cortic osterone concentration and decrease in body temperature. The intraperi toneal administration of SR48692, a non-peptide neurotensin receptor a ntagonist, blocked the neurotensin-induced corticosterone secretion an d significantly reduced the number of neurotensin-induced Fos-positive and Zif268-positive neurons in the amygdaloid complex. A significant positive correlation was found between the number of Fos-positive nucl ei in the central or basolateral nucleus of the amygdala and the serum corticosterone concentration. A significant positive correlation was also found between the number of Zif-positive cells in the paraventric ular nucleus of the hypothalamus and change in body temperature follow ing treatment. Our findings indicate that the central role of neuroten sin in increasing serum corticosterone involves the induction of Fos i n the central and basolateral nuclei of the amygdala. In contrast, the neurotensin-induced hypothermia, which was unaffected by pretreatment with SR48692, involves Zif induction in the paraventricular nucleus o f the hypothalamus. These data support further the existence of centra l neurotensin receptor subtypes which may regulate distinct immediate early genes. Copyright (C) 1996 IBRO. Published by Elsevier Science Lt d.