Distinct effects of sleep deprivation on binding to norepinephrine and serotonin transporters in rat brain

There is evidence to suggest that the antidepressant activity of sleep deprivation may be due to an enhancement of serotonergic and/or noradrenergic neurotransmission in brain. In the present study we examined the possibility that such changes may occur at the level of the norepinephrine (NET) and serotonin (SERT) and transporters. Rats were deprived of sleep for 96 h using the modified multiple platform method and then sacrificed for autoradiographic assessments of NET and SERT binding throughout the brain. [3 H]Nisoxetine binding to the NE transporter was generally decreased in 44 of 45 areas examined, with significant reductions occurring in the anterior cingulate cortex (- 16%), endopiriform n. (- 18%), anterior olfactory n. (- 19%), glomerular layer of olfactory bulb (- 18%), ventral pallidum (- 14%), medial preoptic area (- 16%), retrochiasmatic/arcuate hypothalamus (- 18%), anteromedial thalamic n. (- 15%), and rostral raphe (- 17%). In contrast, SERT binding measured with [C-11]DASB showed no clear directional trends in 61 brain areas examined, but was significantly reduced in subdivisions of the anterior olfactory nucleus (- 22%) and substantia. nigra (- 18%). Thus, sleep deprivation induced widespread decreases in NET binding, and fewer and well-localized decreases in SERT binding. Significant down-regulation in one brain region, the anterior olfactory nucleus, was observed in the case of both transporters. These results suggest that mechanisms involved in the antidepressant action of sleep deprivation may involve generalized NET down-regulation as well as decreased SERT binding in specific areas. Insofar as these changes may be associated with increased levels of serotonin (5-HT) and norepinephrine (NE) in the synapse, they suggest that sleep deprivation may share some basic mechanisms of action with several current antidepressant medications. (C) 2004 Elsevier Inc. All rights reserved.