[Insomnia caused by administration of para-chlorophenylalanine: reversibility by peripheral or central injection of 5-hydroxytryptophan and serotonin]

Abstract

Parachlorophenylalanine (PCPA) produces a total insomnia with a permanent discharge of pontogeniculooccipital (PGO) activity. We studied the reversibility of this insomnia in physiological slow-wave sleep (SWS) and paradoxical sleep (PS) after 5-hydroxytryptophan (5HTP) and serotonin (5HT) administration. Whereas D-5HTP (5 mg/kg) had no effect, parenteral injection of L-5HTP (2.5 mg/kg) or DL-5HTP (5 mg/kg) immediately suppressed PGO activity, then gave rise to the return of SWS and PS with delays of 26 and 60 min, respectively. Intraventricular or intracisternal administration of 5HTP (250 to 1500 micrograms) or 5HT produced physiological sleep with variable delays. If chloramphenicol (which selectively suppresses PS in normal cat) is administered in a PCPA-pretreated cat, 5HTP still suppressed PGO activity and gave rise to a lower amount of SWS but did not restore PS. The results suggest that 5HTP is rapidly decarboxylated into 5HT in restoring the PGO gating effect. Thus, 5HT would seem to act as a classic neurotransmitter. The long latency for PS (and its suppression by chloramphenicol) suggests that 5HT would appear to be a neurohormone controlling another sleep-inducing factor.