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Abstract
The essential amino acid L-tryptophan has been widely used as a sleeping aid because
it can produce drowsiness and decrease sleep latency. Its concentrations in plasma
and brain and its binding to plasma protein are markedly altered in hepatic encephalopathy
and renal failure. The purpose of this investigation was to determine if L-tryptophan
can enhance the sensitivity of the central nervous system to the hypnotic actions
of a barbiturate and an alcohol. Female rats weighing approximately 200 g received
an intravenous infusion of L-tryptophan (0.8 or 0.08 mg/min) for 30 min and then an
infusion of phenobarbital (0.824 mg/min) with L-tryptophan (0.8 or 0.08 mg min-1)
until the onset of loss of righting reflex (LRR). Control animals received an infusion
of saline solution for 30 min and then phenobarbital without the amino acid. Similar
experiments were performed with ethanol (16.3 mg/min), with and without L-tryptophan
(0.8 mg/min). L-Tryptophan infused alone at a rate of 3.8 mg/min for 84 min did not
cause LRR. Administration of L-tryptophan at a rate of 0.8 mg/min with phenobarbital
was associated with statistically significant reductions in the total dose and concentrations
of phenobarbital in serum, serum water, brain, and cerebrospinal fluid (CSF) at onset
of LRR. The 0.08 mg/min infusion of L-tryptophan had a less pronounced effect, with
statistically significant reductions of phenobarbital concentrations at onset of LRR
in brain and CSF. L-Tryptophan also significantly reduced the total dose and the concentrations
of ethanol in serum, brain, and CSF required to produce LRR.(ABSTRACT TRUNCATED AT
250 WORDS)