Distribution of Fos-like immunoreactivity within the rat brain following intraventricular injection of the selective NK(3) receptor agonist senktide.

Abstract

Neurokinin B (NKB) is one member of an evolutionarily conserved family of neuropeptides, the tachykinins. Preferential binding of NKB to endogenous NK(3) receptors affects a variety of biological and physiological processes, including endocrine secretions, sensory transmission, and fluid and electrolyte homeostasis. In light of its widespread biological actions, immunohistochemical detection of the c-Fos protein product was used to study the distribution of neuronal activation in the rat brain caused by intraventricular (icv) injections of the selective NK(3) receptor agonist (succinyl-[Asp(6), N-Me-Phe(8)] substance P [6-11]), senktide. Quantitative analysis revealed that treatment with isotonic saline or 200 ng senktide resulted in the differential expression of Fos-like immunoreactivity (FLI) throughout the brain. Senktide induced the highest number of FLI neurons in the lateral septum, bed nucleus of the stria terminalis, amygdala, paraventricular nucleus of the hypothalamus, median preoptic nucleus, organum vasculosum of the lamina terminalis, supraoptic nucleus, periaqueductal gray, and medial nucleus of the solitary tract compared to isotonic saline controls. Additional regions that contained elevated FLI following icv injection of senktide, relative to saline injection, included the cerebral cortex, lateral hypothalamic nucleus, suprachiasmatic nucleus, ventral tegmental area, substantia nigra, inferior colliculus, locus coeruleus, zona incerta, and arcuate nucleus. Our data indicate that activation of NK(3) receptors induces the expression of FLI within circumscribed regions of the rat brain. This pattern of neuronal activation overlaps with nuclei known to regulate homeostatic processes, such as endocrine secretion, cardiovascular function, salt intake, and nociception.