Positive correlations between cerebral protein synthesis rates and deep sleep in Macaca mulatta.

Local rates of cerebral protein synthesis (ICPSleu) were determined with the autoradiographic L-[1-14C]leucine method in seven awake and seven asleep, adult rhesus monkeys conditioned to sleep in a restraining chair in a darkened, ventilated chamber while EEG, EOG, and EMG were monitored. Prior to the period of measurement all animals slept for 1-4 h. Controls were awakened after at least one period of rapid-eye-movement (REM) sleep. Experimental animals were allowed to remain asleep, and they exhibited non-REM sleep for 71-99% of the experimental period. Statistically significant differences in ICPSleu between control and experimental animals were found in four of the 57 regions of brain examined, but these effects may have occurred by chance. In the sleeping animals, however, correlations between ICPSleu and percent time in deep sleep were positive in all regions and were statistically significant (P < or = 0.05) in 35 of the regions. When time in deep sleep was weighted for the integrated specific activity of leucine in grey matter, positive correlations were statistically significant (P < or = 0.05) in 18 regions in the experimental animals. These results suggest that rates of protein synthesis are increased in many regions of the brain during deep sleep compared with light sleep.

Rapid-eye movement sleep and muscarinic receptor binding in rats are augmented during withdrawal from chronic scopolamine treatment.

The purpose of this study was to determine whether a seven day, once-daily morning administration of scopolamine produces upregulation of muscarinic receptors and augments REMS during withdrawal. After obtaining two, six-hour baseline sleep recordings, beginning at 0900, independent groups of rats were administered either scopolamine or saline every morning for seven days. Six hour sleep recordings were obtained following the first and seventh day of injection and during the two subsequent withdrawal days. After obtaining the last sleep recording the rats were sacrificed and the following brain areas removed: cerebral cortex, hippocampii, caudate nuclei, brainstem, and cerebellum. 3H-QNB was used as the ligand to assess for changes in muscarinic receptor binding. Compared to baseline, scopolamine produced a significant decrease in REMS during the period of drug administration. During the withdrawal days, however, REMS increased during the morning period. Compared to the saline group, the scopolamine treated animals had increased muscarinic receptor binding in the caudate and hippocampus; no significant change in receptor density was observed in the cortex, brainstem or cerebellum.

Hypnogenic center theory of sleep: no support from metabolic mapping in monkeys.

By comparing rates of glucose utilization in brains of monkeys in non-REM sleep and two types of awake controls, we attempted to reveal cerebral hypnogenic centers that drive organisms to sleep through increases in their neural activity. Instead we found that metabolic activity is reduced in all the putative hypnogenic centers during sleep as compared to wakefulness. The results thus offer no support for the notion of an active center that either maintains or triggers sleep.

Behavioral, biochemical and neuroendocrine responses to amphetamine in normal twins and 'well-state' bipolar patients.

An i.v. injection of dextroamphetamine (0.3 mgm/kg) was given to 13 pairs of normal monozygotic twins, three pairs of normal dizygotic twins and 11 patients with bipolar affective disorder in remission and off medications. Behavioral excitation in response to amphetamine was highly correlated in monozygotic twins; it was predicted by the baseline variables of high plasma MHPG, low serum prolactin and low pulse; it correlated with a rise in cortisol; and it was not correlated with plasma amphetamine level. Pre-infusion baseline MHPG and growth hormone and prolactin responses to amphetamine also were concordant in twins. Plasma amphetamine level, pulse and blood pressure and cortisol responses were not concordant, suggesting significant environmental influences. Haloperidol pretreatment in one pair of twins abolished the excitation response but did not reduce increases in cortisol and growth hormone. This suggests a role for dopamine in the excitation response but predominant serotonergic and noradrenergic mediation of the hormonal responses. None of the responses or baseline measures distinguished patients from controls. Thus, no consistently altered sensitivity to monoaminergic stimulation by amphetamine in bipolar affective disorder was demonstrated in this study. This is one of the first reports of familial (possibly genetic) variation in a psychostimulant drug response in man. The responses identified as concordant may be useful in characterizing other pathologic conditions.