A GABAergic habenulo-raphe pathway mediates both serotoninergic and hypnogenic effects of vasotocin in cats

Extremely small amounts (10(-4) pg) of the pineal nonapeptide arginine vasotocin (AVT), injected into the pineal recess of freely moving cats, decreased the levels of 5-hydroxyindole acetic acid (5-HIAA) in the raphe dorsalis nucleus and induced slow wave sleep. In cats with lesions in the lateral habenula, 10(-4) pg AVT injected into the pineal recess, failed to decrease raphe dorsalis 5-HIAA levels and to induce slow wave sleep. The GABA antagonist picrotoxin (1 ng) injected into the pineal recess 15 min before the administration of AVT (10(-4) pg), completely prevented AVT from decreasing raphe dorsalis 5-HIAA levels and from inducing slow wave sleep. A highly significant correlation could be established between the decrease of raphe dorsalis 5-HIAA levels and the induction of slow wave sleep. No changes in raphe dorsalis 5-HIAA levels could be detected in cats injected with 10(-4) pg AVT into the lateral or into the fourth ventricle. Neither arginine vasopressin nor oxytocin (10(-4) pg) injected into the pineal recess, could alter raphe dorsalis 5-HIAA levels. It is concluded that AVT induces slow-wave sleep in cats by activating an inhibitory GABAergic lateral habenula-raphe dorsalis pathway.