Abstract
Rapid eye movement (REM) sleep deprivation induces several behavioral changes. Among these, a decrease in yawning behavior produced by low doses of cholinergic agonists is observed which indicates a change in brain cholinergic neurotransmission after REM sleep deprivation. Acetylcholinesterase (Achase) controls acetylcholine (Ach) availability in the synaptic cleft. Therefore, altered Achase activity may lead to a change in Ach availability at the receptor level which, in turn, may result in modification of cholinergic neurotransmission. To determine if REM sleep deprivation would change the activity of Achase, male Wistar rats, 3 months old, weighing 250-300 g, were deprived of REM sleep for 96 h by the flower-pot technique (N = 12). Two additional groups, a home-cage control (N = 6) and a large platform control (N = 6), were also used. Achase was measured in the frontal cortex using two different methods to obtain the enzyme activity. One method consisted of the obtention of total (900 g supernatant), membrane-bound (100,000 g pellet) and soluble (100,000 g supernatant) Achase, and the other method consisted of the obtention of a fraction (40,000 g pellet) enriched in synaptic membrane-bound enzyme. In both preparations, REM sleep deprivation induced a significant decrease in rat frontal cortex Achase activity when compared to both home-cage and large platform controls. REM sleep deprivation induced a significant decrease of 16% in the membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) in the 100,000 g pellet enzyme preparation (home-cage group 152.1 +/- 5.7, large platform group 152.7 +/- 24.9 and REM sleep-deprived group 127.9 +/- 13.8). There was no difference in the soluble enzyme activity. REM sleep deprivation also induced a significant decrease of 20% in the enriched synaptic membrane-bound Achase activity (home-cage group 126.4 +/- 21.5, large platform group 127.8 +/- 20.4, REM sleep-deprived group 102.8 +/- 14.2). Our results suggest that REM sleep deprivation changes Ach availability at the level of its receptors through a decrease in Achase activity.
Highlights
Rapid eye movement (REM) sleep deprivation induces several behavioral changes in rats [1], among them a decrease in yawning behavior induced by low doses of cholinergic agonists [2,3] indicating alteration in cholinergic sensitivity
The results obtained in this study showed that REM sleep deprivation resulted in a consistent decrease in membrane-bound Achase activity in rat frontal cortex, but not in total cerebral cortex
This change was detected when REM sleep-deprived animals were compared with the large platform group, suggesting a specific effect of REM sleep deprivation rather than a general effect of stress on Achase activity in the rat frontal cortex
Summary
Rapid eye movement (REM) sleep deprivation induces several behavioral changes in rats [1], among them a decrease in yawning behavior induced by low doses of cholinergic agonists [2,3] indicating alteration in cholinergic sensitivity. It is claimed that REM sleep deprivation has an antidepressant effect [4] and cholinergic neurotransmission has been proposed to be implicated in depression [5,6]. These findings suggest a change of cholinergic neurotransmission after REM sleep deprivation. The frontal cortex is involved in many aspects of behavior Lesions in this region result in changes of social and affective behaviors [7]. Since some authors report a decrease in REM sleep in animals with NBM lesions [18,19], it is of interest to evaluate the cholinergic projections from NBM after REM sleep deprivation
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