Lai YY, Hsieh KC, Nguyen D, Siegel JM (2008) The substantia nigra and the control of sleep. Neuroscience 2008 Abstracts 586.9/SS42. Society for Neuroscience, Washington, DC.
Summary: It has been established that the substantia nigra (SN) is involved in the control of motor activity. However, its role in the regulation of sleep remains unclear. We have previously found that NMDA lesions in the SN suppress sleep in the cat. A recent study demonstrated that lesions of the SN by hypocretin2-saporin result in severe insomnia in the rat. Thus, we hypothesized that activation of the SN by application of either excitatory transmitter analogs/agonists or GABA receptor blockers would induce sleep. Hypocretin had been reported to exert an excitatory effect on SN neuronal activity. The SN receives dense projections from hypocretin neurons. In the current study, we investigated whether microinfusion of hypocretin into the SN would modulate sleep and wakefulness in freely moving rats. Adult male Sprague-Dawley rats were implanted with EEG and EMG electrodes, and a guide cannula targeting the SN. Experiments were conducted one week after the rat had been implanted. The rats were housed individually in sound-attenuated chambers in LD 12:12. Hypocretin-1 was delivered via microdialysis probes (CMA/11) at a rate of 2 μL/min. Each one-hour of hypocretin infusion (ZT4 to ZT5 in the light period) was preceded by a 2-hour baseline period of artificial cerebrospinal fluid (aCSF) infusion and was followed by a 2-hour aCSF infusion. The lower concentration of hypocretin-1 (36 μM, n=2) reduced wakefulness by 19% ± 9.5% and increased slow wave sleep (SWS) by 12.8% ± 2.3% of the baseline level. The higher concentration of hypocretin-1 (72 μM, n=3) reduced wakefulness by 30.5% ± 16.4% of the baseline level and produced an increase in both SWS and REM sleep, by 10.2% ± 2.2% and 63.7% ± 26.6% respectively. The increased sleep induced by both concentrations of hypocretin were also observed in the first post-infusion hour. In conclusion, we found that hypocretin-1 has a sleep-promoting effect in the SN. Our previous study showed that hypocretin (orexin) neurodegeneration occurred in Parkinson’s disease patients. This finding suggests that sleep difficulties in Parkinson’s disease patients may result from a combination of lesions in the SN and the secondary effects of the loss of hypocretin neurons.
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