PINEAL VASOTOCIN AND SLEEP - INVOLVEMENT OF SEROTONIN CONTAINING NEURONS

Extremely small amounts (10-4 pg) of arginine vasotocin (AVT) injected into the third ventricle of unanesthetized cats induce non-rapid eye movement (NREM) sleep and suppress rapid eye movement (REM) sleep. The same amount (10-4 pg) of intraventricularly injected AVT increased at 15 and 30 min 5-hydroxytryptamine (5-HT) and decreased at 30 and 60 min 5-hydroxyindole acetic acid (5-HIAA) levels of the brain. Fluoxetine, a specific 5-HT uptake inhibitor, greatly enhanced the NREM sleep induced by AVT. Neither arginine vasopressin, nor oxytocin at the doses used (10-4 pg), was able to affect indole levels of the brain or to enhance NREM sleep and to suppress REM sleep after fluoxetine, demonstrating the high specificity of AVT effects. Methergoline, a selective central 5-HT receptor blocker, completely prevented AVT induction of NREM sleep. Extremely small amounts of AVT (10-6 pg), which in some cats were unable to induce NREM sleep and to suppress REM sleep, become effective after pretreatment with small amounts of 5-hydroxytryptophan (5-HTP). It is suggested that AVT induces NREM sleep and suppresses REM sleep by interfering with 5-HT release at postsynaptic receptor sites. The present results strongly support the monoaminergic theory of sleep providing the first evidence that a peptide synthesized by the brain induces sleep by a serotoninergic mechanism. © 1979.