Nitric oxide and sleep in the rat: a puzzling relationship
Section snippets
Animals and drugs
The protocol of this study was approved by the French Ministry of Agriculture (no. 03-505), and efforts were made to minimize animal suffering and to reduce the number of animals used. Male Sprague–Dawley (Iffa–Credo, l'Arbresle, France) rats weighing 250–350 g were used in this study. l-NAME (Sigma) was dissolved in 0.9% NaCl and the pH adjusted to 7.2 with NaOH. For i.p. injections, 7-NI (Tocris Cookson) was suspended in peanut oil (Sigma) by sonication, while for local microinjections, it was
Nitric oxide voltammetric measurements
l-NAME administered i.p. did not induce significant variations in the voltammetric NO signal measured in the cortex of anesthetized rats. This lack of effect persisted for at least 80 min, even when the highest dose of the inhibitor (200 mg/kg) was administered (Fig. 1).
Polygraphic recordings
The i.p. administration of l-NAME (100 mg/kg), at the beginning of the dark period, was followed by an important increase in the amounts of SWS and PS. The effects started 1 h after the injection and remained constant over the
Discussion
The main findings obtained in this study indicate the following:
- 1.
The i.p. administration of the non-selective NOS inhibitor, l-NAME, at 100 mg/kg, does not influence the cortical release of NO measured by voltammetry, but enhances the durations of both SWS and PS.
- 2.
The i.p. administration of the selective nNOS inhibitor, 7-NI, at 40 mg/kg, produces a long-lasting decrease in the cortical release of NO and reduces duration of PS.
- 3.
Intra-DRN microinjections of either l-NAME or 7-NI (100 ng in 0.20 ml)
Conclusion
The present findings are in agreement with other studies, which proposed that an intact NO-synthesizing system is required for normal sleep regulation. However, the data reported here underline the existence of a dual role for NO in sleep–wake cycle regulation, i.e. a sleep-inhibiting influence of peripheral origin and a PS-facilitating role at the central level, notably for the NO–5-HT component of the DRN. In view of the great complexity of the anatomical elements of the brain synthesizing
Acknowledgements
This research was supported by INSERM, CNRS, Rône-Alpes region and Fondation pour la Recherche Médicale 98. We also thank C. Limoge for improving the English text and G. Debilly for statistical analysis.
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