C-FOS expression in the rat brain in response to substance P and neurokinin B

Substance P, the principal neurokinin peptide in the mammalian brain and th e natural ligand for the NK1 tachykinin receptor, plays an integrative role in the regulation of cardiovascular, neuroendocrine and behavioural. respo nses to stress. In rats, stimulation of periventricular NK1 receptors in th e forebrain induces a distinct pattern of cardiovascular responses which is accompanied by intense grooming behaviour. Ligands for NK3 receptors induc e a different pattern of cardiovascular and behavioural responses which com prises an increased release of vasopressin from the posterior pituitary and wet-dog shakes behaviour. To define the brain areas in the rat which respo nd to stimulation of forebrain NK1 and NK3 receptors and participate in the generation of these responses, the induction of c-Fos immunoreactivity was examined in brains following intracerebroventricular injections of substan ce P and neurokinin B in conscious rats. Stimulation of central NK3 recepto rs by substance P (25, 100 and 500 pmol) injected into the lateral ventricl e elicited grooming behaviour (face washing and hind limb grooming) and res ulted in a marked c-Fos expression in the paraventricular, dorsomedial and parabrachial nuclei and in the medial thalamus. At 25 pmol, substance P did not significantly increase c-Fos expression, at 100 pmol, maximal c-Fos ac tivation was induced in all four brain regions which responded to the pepti de. Intracerebroventricular pretreatment of rats with the selective and hig h-affinity, non-peptide NK1 receptor antagonist, RP 67580 (500 pmol), but n ot with its inactive enantiomer, RP 68651, completely abolished the behavio ural response to substance P and reduced the substance P-induced c-Fos expr ession in all brain areas to nearly control levels. Intracerebroventricular injection of the natural ligand for NK3 receptors, neurokinin B (500 pmol) , elicited wet-dog shakes behaviour and activated c-Fos expression in local ized regions of the forebrain including the organum. vasculosum. laminae te rminalis, subfornical organ, median preoptic nucleus, paraventricular, supr aoptic and anterior hypothalamic nuclei, medial thalamus and in the ventral tegmental area. These results demonstrate that the neurokinins, substance P and neurokinin B, induce specific and different patterns of c-Fos express ion in distinct regions of the rat brain. Brain areas which selectively res ponded to substance P have been traditionally linked to the central regulat ion of cardiovascular and neuroendocrine reactions to stress or involved in the processing of nociceptive responses. On the other side, brain areas ac tivated by neurokinin B are known to be involved in the central regulation of blood pressure, water and salt homeostasis or control of behaviour. (C) 2001 Elsevier Science B.V. All rights reserved.