EFFECTS OF CHRONIC SLEEP-DEPRIVATION ON CENTRAL CHOLINERGIC RECEPTORSIN RAT-BRAIN

Rats subjected to chronic total sleep deprivation (TSD) by the disk-ov er-water method have shown very large, sustained rebounds in paradoxic al sleep (PS) (also known as REM sleep). Other studies have indicated that cholinergic mechanisms are involved in the instigation and mainte nance of PS. Hypothetically, the large PS rebounds could be mediated b y an upregulation of cholinergic receptors during TSD. To evaluate thi s hypothesis, regional brain cholinergic receptors were compared in ra ts subjected to 10-day TSD by the disk-over-water method (TSD rats), y oked control (TSC) rats which received the same physical stimulation b ut with much smaller reductions in sleep, and home cage control (HCC) rats. L-[H-3]nicotine and [H-3]quinuclidinyl benzilate were used as sp ecific cholinergic radioligands for nicotinic and muscarinic receptor binding assays, respectively. Nicotinic receptor binding was not signi ficantly different among groups for any of the brain regions assayed, including frontal cortex, parietal cortex, thalamus, amygdala, hippoca mpus, anterior hypothalamus, posterior hypothalamus, caudate, limbic s ystem (including septal area, olfactory tubercle, and nucleus accumben s), midbrain, pens, and medulla. Thus, there was no evidence that chan ges in nicotinic receptors mediate the PS rebounds. For muscarinic rec eptor binding, TSD rats differed significantly from control rats only in showing a higher binding affinity than TSC rats in the limbic syste m and a lower binding density than;HCC rats in the hippocampus. On the other hand, significant differences in muscarinic receptor binding si tes between rats selectively deprived of PS and their yoked controls w ere found only for the septal area. Although chronic sleep deprivation resulted in a few regionally specific changes in muscarinic receptor binding, compared to the large PS rebounds during recovery from chroni c sleep deprivation, the changes in receptor binding were very small a nd were not apparent in the region most intimately related to the chol inergic instigation of PS, i.e., the pons. Thus, there was no substant ial evidence that PS rebounds are mediated via cholinergic receptor up regulation.