Inhibition of Release of Corticotropin Releasing Hormone in Cats by Extremely Small Amounts of Vasotocin Injected into the Third Ventricle of the Brain. Evidence for the Involvement of 5-Hydroxytryptamine-Containing Neurons

Abstract

A single injection of 10-6 pg synthetic arginine vasotocin (AVT), corresponding to about 600 molecules AVT, into the 3rd ventricle of urethane-anesthetized cats, significantly decreased plasma cortisol levels between 15 and 60 min after injection. A partially purified bovine pineal AVT injected into the 3rd ventricle in an equivalent amount produced the same effects. After incubation with trypsin, pineal AVT completely lost its ability to decrease plasma cortisol levels. In the range tested, effects of synthetic AVT appear dose-dependent since 10-5 pg caused a more pronounced effect than 10-6 pg, and 10-7 pg only slightly decreased plasma cortisol levels. Neither synthetic arginine vasopressin nor oxytocin, injected into the 3rd ventricle in the amount of 10-6 pg, was able to affect plasma cortisol levels. When 10-6 pg of synthetic AVT was injected into the lateral ventricle of the brain, infundibular recess or into the pituitary, no effect on plasma cortisol levels could be detected. The same amount of synthetic AVT, injected into the 3rd ventricle of cats, treated 48 h earlier with p-chlorophenylalanine (p-CPA), failed to decrease plasma cortisol levels. Administration of 5-hydroxytryptophan (5-HTP) to p-CPA-treated cats 1 h before intraventricular injection of AVT partially restored ability of AVT to decrease plasma cortisol levels. The hypothalamic 5-hydroxytryptamine (5-HT) content of cats increased significantly at 30 min after injection of 10-5 pg synthetic AVT into the 3rd ventricle. The same amount of vasopressin or oxytocin injected into the 3rd ventricle was unable to affect hypothalamic 5-HT content. Increase of plasma cortisol levels induced by a crude corticotropin releasing factor (CRF) injected into the pituitary was not significantly affected by the previous intraventricular injection of AVT. Apparently AVT injected into the 3rd ventricle of cats decreased plasma cortisol levels by inhibiting corticotropin releasing hormone (CRH) synthesis and/or release, and mammalian brain contains the most sensitive receptors for AVT so far described. These receptors may be 5-HT containing neurons.