Reduction of rapid eye movement (REM) sleep by glucose alone or glucose and insulin in rats

Abstract

Administration of a high dose of glucose (2.5 g/kg, i.p.) that is known to produce severe hyperglycemia in euglycemic rats suppressed rapid eye movement (REM) sleep time significantly during the first three hours of 8 hr total electroencephalogram (EEG) recording period. Co-administration of glucose (2.5 g/kg, i.p.) and a non-convulsive dose of insulin (1.0 I.U./kg, i.p.) produced a significant reduction in REM sleep time during 1st through 5th hour and an increase in slow-wave sleep (NREM) time in the 3rd and 4th hour of 8 hr total EEG recording period. However, awake, NREM and REM sleep time in the 8 hr total EEG recording period were unaffected by either glucose alone or glucose plus insulin treatments. These results strongly suggest that the insulin's effects on the sleep-awake cycle i.e. reduction in REM and a slight increase in NREM sleep times of rats is not due to indirect effects of insulin on the central nervous system via hypoglycemia as reported by us previously, but could possibly be due to its direct effects on brain chemistry of neurotransmitters such as serotonin, catecholamines and acetylcholine which are believed to modulate the sleep-awake cycle pattern in rats. The concentration and metabolism of brain serotonin is related directly to the plasma and brain concentration of its precursor, tryptophan (1–2). Both insulin and the concentration of free plasma tryptophan stimulate tryptophan uptake from blood to brain (3–5). Subconvulsive doses of insulin and insulin, endogenously secreted following the consumption of carbohydrate diet increased the concentrations of both brain tryptophan and serotonin in rats (6). Serotonin containing neurons are likely to play a role in the control of sleep, thermoregulation, motor activity, food consumption, pain perception and sexual activity (6–9). If the concentration and metabolism of serotonin in the brain is insulin dependent, the hormone should also affect serotonin dependent neurobehavioural functions including sleep-awake cycle. Our previous study showed that intraperitoneal administration of a non-convulsive dose of insulin suppressed rapid eye movement (REM) sleep time and produced a slight but significant increase in slow-wave sleep time (NREM) in rats (10). These changes in sleep-awake cycle correlated with insulin induced hypoglycemia (10). Therefore, the question could be raised whether the insulin induced reduction in REM sleep time and elevation of NREM sleep time in rats was indirect through its hypoglycemic effects or if it was direct through changes in the chemistry of various putative neurotransmitters, such as serotonin, catecholamines and acetylcholine of sleep-awake cycle (11–19). The present study was designed to investigate the effects of glucose alone or combination of glucose and insulin on sleep-awake cycle of rats.