OXYTOCIN PATHWAYS MEDIATE THE CARDIOVASCULAR AND BEHAVIORAL-RESPONSESTO SUBSTANCE-P IN THE RAT-BRAIN

Stimulation of brain periventricular and hypothalamic substance P rece ptors induces a presser response and tachycardia associated with mesen teric and renal vasoconstriction and hindlimb vasodilation resembling thus the classical defense reaction. This cardiovascular response is b rought about by the activation of the sympathoadrenal system and is ac companied by grooming behavior. To address the role of oxytocinergic p athways in the brain in the mediation of these responses, we investiga ted the effects of central pretreatment of rats with oxytocin antisens e, mixed base, and sense oligodeoxynucleotides on mean arterial pressu re, heart rate, and grooming behavior induced by intracerebroventricul ar injections of substance P (50 pmol). Central pretreatment of consci ous rats with the oxytocin antisense oligodeoxynucleotide (intracerebr oventricular injections, 8 and 4 hours before administration of substa nce P) attenuated the mean arterial pressure (by 55%) and heart rate r esponses (by 58%) as well as grooming behavior induced by the peptide. A complete recovery of all substance P-induced responses was observed 28 hours after antisense oligodeoxynucleotide pretreatment. Intracere broventricular pretreatment of rats with mixed base and sense oligodeo xynucleotides did not affect the cardiovascular and behavioral respons es to substance P. The signal for oxytocin mRNA in the paraventricular nucleus was reduced only in rats pretreated with the antisense oligod eoxynucleotide. These results demonstrate that oxytocin neurons in the paraventricular nucleus, which innervate the cardiovascular centers i n the hindbrain and the spinal cord, mediate the increases in blood pr essure and heart rate induced by stimulation of substance P receptors in the forebrain. These neurons may also transmit signals, which are g enerated by substance P in the hypothalamus and are responsible for th e sympathoadrenal activation in response to stress.