Long-lasting insomnia induced by preoptic neuron lesions and its transient reversal by muscimol injection into the posterior hypothalamus in the cat

Abstract

In order to analyse the role of the anterior hypothalamus in the regulation of the sleep-waking cycle we made bilateral neuronal lesions at different levels of the anterior hypothalamus in cats, by means of microinjections of a cell-specific neurotoxin:ibotenic acid. These lesions resulted in severe insomnia in eight cats. This insomnia was characterized by a large decrease or even disappearance of paradoxical sleep and deep slow wave sleep and, to a lesser extent, by a decrease of light slow wave sleep, for 2-3 weeks. In the other five animals, we observed a large reduction of deep slow wave sleep (0-40% of control level), but a less intensive decrease of time spent in paradoxical sleep (50-75% of control level) and no marked effect on light slow wave sleep. During the first 3-6 postoperative days we also noticed hyperthermia in all cats; thereafter, the animals presented only a slight increase in brain temperature which did not appear to trigger the sleep impairment. Histological analysis of the different lesions revealed that the insomnia could be attributed to neuronal cell body destruction in the mediobasal part of the anterior hypothalamus covering; the medial preoptic area and a narrow portion of the lateral preoptic area as well as a restricted part of the anterior hypothalamic nucleus. In order to investigate the putative role of the posterior hypothalamic structures in the mechanism of insomnia after lesion of the mediobasal preoptic area neurons we injected an agonist of GABA into the ventrolateral part of the posterior hypothalamus to locally depress the neuronal activity. The bilateral intracerebral microinjection of muscimol (0.5-5 micrograms) induced a transient intensive hypersomnia (slow wave sleep and paradoxical sleep). These findings indicate that neuronal cell loss in the mediobasal preoptic area induced a long lasting insomnia. Thus, it may be hypothesized that the integrity of this structure is necessary for sleep appearance. Finally, our data are in keeping with an intrahypothalamic regulation of the sleep-waking cycle.