A GABAergic habenulo-raphe pathway mediation of the hypnogenic effects of vasotocin in cat.

Electrolytic lesions, performed in the lateral habenula of cats, specifically altered the sleep-wakefulness cycle and completely prevented the usual actions of intraventricularly administered vasotocin, which are to induce non-rapid eye movement sleep and to suppress rapid eye movement sleep. These alterations are (i) selectively related to lateral habenula, since similar lesions performed in thalamus 2 mm lateral to lateral habenula, were unable to prevent the actions of vasotocin or to reproduce the sleep alterations observed after habenular lesions, and (ii) reversible, since at eight days after habenular lesions there is a total return to normal of the sleep-wakefulness parameters, and vasotocin is able again to induce its hypnogenic effects. Opposite effects, characterized by an increase in non-rapid eye movement sleep and a decrease in rapid eye movement sleep, could be induced by a short (10 min) electrical stimulation of the lateral habenula, but not if the stimulating electrodes are placed 2 mm more laterally. Picrotoxin, a gamma-aminobutyrate antagonist, injected intraventricularly in normal cats was without any apparent effect on the sleep-wakefulness cycle if administered in a dose of 1 ng, but had sleep-increasing effects when administered in a dose of 100 ng. However, the smaller dose of picrotoxin (1 ng), when administered 15 min before vasotocin, completely blocked the hypnogenic effect of vasotocin. It is suggested that vasotocin acts within the brain by activating a descending gamma-aminobutyrate-containing habenulo-raphe pathway, and that this pathway plays an important role in the induction and/or organization of the sleep-wakefulness cycle.