Inhibition of Release of Luteinizing Hormone in the Male Rat by Extremely Small Amounts of Arginine Vasotocin: Further Evidence for the Involvement of 5-Hydroxytryptamine-Containing Neurons in the Mechanism of Action of Arginine Vasotocin

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Abstract
A single injection of 10-4 pg synthetic arginine vasotocin (AVT) into the third ventricle of urethane anesthetized male rats, significantly decreased plasma LH levels between 15–60 min after the injection, while plasma FSH levels remain unchanged. At 120 min, plasma LH levels returned to their preinjection levels. In the range tested, the effects of AVT seem to be dose dependent, because 10-5 pg induce a less pronounced decrease of plasma LH levels than 10-4 pg, and 10 pg did not decrease plasma LH levels. No effects on plasma LH levels could be detected when amounts of AVT between 10-1–10-4 pg were injected into the pituitary. Neither synthetic arginine vasopressin nor oxytocin, injected into the third ventricle in amounts between 10-3–10-4 pg, was able to affect plasma LH levels. The increase of plasma LH levels induced by exogenous LHRH was not significantly affected by the previous intraventricular injection of AVT. When 10-4 pg AVT were injected into the third ventricle of rats treated 48 h earlier with p-chlorophenylalanine (p-CPA), no effects on plasma LH levels could be detected. Administration of 5-hydroxytryptophan to p-CPA-treated rats, 1 h before the injection of AVT partially restored the ability of AVT to decrease plasma LH levels. The hypothalamic 5-hydroxytryptamine (5-HT) content of normal rats as well as that of rats treated with p-CPA and 5-hydroxytryptophan significantly increased at 30 min after the intraventricular injection of 10-4 pg AVT. No effects on hypothalamic 5-HT content could be detected after the intraventricular injection of 10-4 pg AVT in rats treated with p-CPA alone. The results of the present work suggest that AVT injected into the third ventricle of male rats at the lowest effective concentrations so far reported for an active biological substance decreases plasma LH levels by inhibiting the release of LHRH in the brain and not by interfering directly with the release of LH at the pituitary level. Evidence is provided that AVT induces these effects by interfering with 5- HT neurotransmission in the brain.