Effects of chronic sleep deprivation on central cholinergic receptors in rat brain.
Rats subjected to chronic total sleep deprivation (TSD) by the disk-over-water method have shown very large, sustained rebounds in paradoxical sleep (PS) (also known as REM sleep). Other studies have indicated that cholinergic mechanisms are involved in the instigation and maintenance of PS. Hypothetically, the large PS rebounds could be mediated by an upregulation of cholinergic receptors during TSD. To evaluate this hypothesis, regional brain cholinergic receptors were compared in rats subjected to 10-day TSD by the disk-over-water method (TSD rats), yoked control (TSC) rats which received the same physical stimulation but with much smaller reductions in sleep, and home cage control (HCC) rats. L-[3H]nicotine and [3H]quinuclidinyl benzilate were used as specific cholinergic radioligands for nicotinic and muscarinic receptor binding assays, respectively. Nicotinic receptor binding was not significantly different among groups for any of the brain regions assayed, including frontal cortex, parietal cortex, thalamus, amygdala, hippocampus, anterior hypothalamus, posterior hypothalamus, caudate, limbic system (including septal area, olfactory tubercle, and nucleus accumbens), midbrain, pons, and medulla. Thus, there was no evidence that changes in nicotinic receptors mediate the PS rebounds. For muscarinic receptor binding, TSD rats differed significantly from control rats only in showing a higher binding affinity than TSC rats in the limbic system and a lower binding density than HCC rats in the hippocampus. On the other hand, significant differences in muscarinic receptor binding sites between rats selectively deprived of PS and their yoked controls were found only for the septal area.(ABSTRACT TRUNCATED AT 250 WORDS)
Tsai
L L
LL
Department of Psychiatry, University of Chicago, IL 60637.
Bergmann
B M
BM
Perry
B D
BD
Rechtschaffen
A
A
D000818:Animals; D001921:Brain / Q000378:metabolism*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012892:Sleep Deprivation / Q000502:physiology*; D012895:Sleep, REM / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation
D011950:Receptors, Cholinergic