Reversibility of Para-chlorophenylalanine-induced insomnia by intrahypothalamic microinjection of l-5-hydroxytryptophan

Abstract Para -chlorophenylalanine, a blocker of serotonin biosynthesis by inhibiting tryptophan hydroxylase, induced total insomnia which was accompanied in cat by a permanent discharge of ponto-geniculo-occipital activity. l -5-Hydroxytryptophan microinjection (1–4 μg/0.5 μl) in the anterior hypothalamus 72 h after para -chlorophenylalanine administration, restored both slow wave sleep and paradoxical sleep with variable latencies for each state of sleep. On the contrary, ponto-geniculo-occipital activity was never suppressed. The hypnogenic effects of l -5-hydroxytryptophan were always followed by a return of the para -chlorophenylalanine-induced insomnia. On the other hand, the temperature recording did not show any alteration of the cerebral temperature after para -chlorophenylalanine treatment but the subsequent l -5-hydroxytryptophan microinjection was followed by hyperthermia. Using immunohistochemistry for serotonin after intrahypothalamic l -5-hydroxytryptophan microinjection in para chlorophenylalanine-pretreated cat, we defined a restricted region of the anterior hypothalamus possibly responsible for the hypnogenic effect. This region included the lateral hypothalamus and the anterior hypothalamic area. It is suggested that the reversible hypersomnia after l -5-hydroxytryptophan microinjection in the anterior hypothalamus in para -chlorophenylalanine-pretreated cat is due to a neurohormonal action of serotonin: serotonin could act upon the anterior hypothalamus which secondarily inhibits a waking system located in the ventrolateral hypothalamus leading to the appearance of paradoxical sleep.