SUBSTANCE P AND STRESS RELATED REM SLEEP REBOUND IN RAT

Cespuglio Raymond
INSERM unit 480, C. Bernard University, 8, av. Rockefeller, F-69373 Lyon - France
Email: cespuglio@univ-lyon1.fr

Results as yet obtained in animals indicate that an immobilisation stress (IS) of short duration is followed by a REM sleep rebound which occurrence is ensured by reciprocal interactions between the dorsal pontine tegmentum and the basal hypothalamus. It is now also known that endogenous depression is accompanied by constant modifications of sleep and that short lasting mood improvements are obtained by REM sleep deprivation. Furthermore, in a recent trial conducted with depressed patients, robust antidepressant effects of a Substance P receptors antagonist have been reported. But, mechanisms of therapeutic effect, while suggested stress-related still remain unknown. The present investigation was conducted in order to determine whether the Substance P component of the dorsal pontin tegmentum plays a critical role in the genesis of the sleep rebound occurring after an immobilisation stress in the rat.

Polygraphic data obtained confirm that the 1h IS applied at the beginning of the dark period is followed by a REM sleep rebound (+59%/11h of the dark period). When the animals are pre-treated with a Substance P receptors antagonist, the stress related REM sleep rebound is suppressed without marked alterations of the basal sleep levels. Immunohistochemical labellings performed in the pontine tegmentum show that Substance P perykaria are present in the LDT, the rostro-dorsal part of the nRD and the periacqueductal grey. Clear contacts exist between CLIP nerve endings and Substance P neurons in the LDT. Finally, the RIA for Substance P performed indicates that the peptide concentration is significantly increased in the LDT at the end of the restraint (+ 23 %) and that its increase is suppressed when the animals are pre-treated with a Substance P receptors antagonist.

According to the data reported here and in the literature, it appears likely that the stress response relayed by CLIP in LDT and nRD might involve Substance P. This compound, through a complex pontine neuronal network and NK1 receptors might constitute a final and determinant step in the cascade of events conducting to the expression of the stress related sleep rebound. The fact that Substance P receptors antagonists are capable to suppress this rebound might constitute, at least partly, a determinant mechanism through which these compounds relieve depression in humans.

Acknowledgements : This work was supported by Inserm and C. Bernard University.