Serotonin (5-HT) has a role in regulating behavioral state and controlling the production of ponto-geniculo-occipital (PGO) waves, though the exact mechanism of action is not known. The most prevailing explanation is that 5-HT exerts its influence on behavioral state and PGO waves by inhibiting and disinhibiting cholinergic cells in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT), which have been implicated in their generation. Recent work in rats has demonstrated 5-HT₂ receptors on most cholinergic cells in PPT/LDT. We microinfused the relatively specific 5-HT₂ agonist, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane), the relatively specific 5-HT₂ antagonist, ketanserin, and the nonspecific 5-HT antagonist, methysergide, locally into the peribrachial region of PPT in cats and monitored behavioral state and PGO waves. Neither drug significantly affected behavioral state or PGO wave activity. These results suggest that 5-HT₂ receptors associated with cholinergic cells are minimally involved in the control of behavioral state and, together with the recent findings of others, suggest that 5-HT may not modulate PGO wave generation via direct action on cholinergic neurons in PPT/LDT, a departure from the long-held but minimally-tested view.

Sleep Research Online

Changes in sleep were studied during 6 hours after intracerebroventricular (ICV) administration of Insulin-like growth factor-1 (IGF-1) or the structurally related insulin. IGF-1 was injected either at dark onset (0.05 or 0.5 µg) or 6 hours after light onset (0.05, 0.5, or 5.0 µg). The small dose of IGF-1 consistently, albeit modestly, enhanced NREMS over the 6 hour postinjection period in both the dark and the light cycles (REMS increased only at night). The NREMS-promoting activity vanished when the dose was increased to 0.5 µg, and 5.0 µg IGF-1 elicited a marked and prompt suppression in NREMS. Heat-inactivated IGF-1 (0.05 µg) did not alter sleep. On a molar base, the NREMS-promoting dose of insulin was higher than that of IGF-1. Late (hours 7-17 postinjection) enhancements in EEG slow wave activity during NREMS were observed after 5.0 µg IGF-1. The results indicate that IGF-1 can promote NREMS and may contribute to the mediation of the effects of GH on sleep. The acute sleep-suppressive activity of the high dose of IGF-1 is attributed to an inhibition of endogenous growth hormone-releasing hormone (GHRH).

Sleep disturbances of alcoholics while actively drinking and at the beginning of, and during, abstinence were frequently reported. Recently, Gillin et al. (1994) showed that a high "REM sleep pressure" at the time of admission to a 1-month inpatient alcohol treatment program predicted the relapse in nondepressed patients with primary alcoholism at 3 months following hospital discharge. We investigated 24 patients with primary alcoholism after 2-3 weeks abstinence in the sleep laboratory; in 15 of these patients the cholinergic REM sleep induction test (CRIT) with 10 mg galanthamine was performed additionally. In comparison with an age- and sex-matched healthy control group, patients had a heightened "REM sleep pressure" including shortened REM latency and increased REM density. A decrease of serotonergic neurotransmission is proposed as being the neurochemical mechanism to explain the results in alcoholic subjects. Follow-up investigations will clarify whether the sleep abnormalities in alcoholism are state- or trait-markers and whether they are suitable to predict the relapse risk.

Sleep Research Online

High and monotonically declining levels of EEG slow wave activity (SWA) occur following arousal from hibernation. Similar profiles of SWA occur in mammals including humans during sleep following periods of prolonged wakefulness, and have been interpreted as reflecting a homeostatic process regulating NREM sleep. It was proposed that even though hibernation appears to be an evolutionary extension of NREM sleep, the low brain temperatures during hibernation are not compatible with sleep restorative processes, and therefore sleep debt accumulates during hibernation and may be a factor triggering periodic arousal. In the present study, golden-mantled ground squirrels were sleep deprived by gentle handling following arousal from hibernation. If the SWA peaks following bouts of hibernation reflect a homeostatic response to an accumulated sleep debt, sleep deprivation should simply displace the SWA which would then occur, and be augmented, during subsequent sleep. In contrast, when animals were sleep deprived following arousal from hibernation, the anticipated SWA peak did not occur during subsequent sleep. It is suggested that the SWA following arousal from hibernation does not represent homeostatic regulation of NREM sleep, but instead some other neurological process involved in the recovery of brain function from an extended period at low temperature.

Sleep Research Online