TY - JOUR T1 - Altered Sleep Homeostasis after Restraint Stress in <em>5-HTT</em> Knock-Out Male Mice: A Role for Hypocretins JF - The Journal of Neuroscience JO - J. Neurosci. SP - 15575 LP - 15585 DO - 10.1523/JNEUROSCI.3138-09.2009 VL - 29 IS - 49 AU - Adeline Rachalski AU - Chloé Alexandre AU - Jean-François Bernard AU - Françoise Saurini AU - Klaus-Peter Lesch AU - Michel Hamon AU - Joëlle Adrien AU - Véronique Fabre Y1 - 2009/12/09 UR - http://www.jneurosci.org/content/29/49/15575.abstract N2 - Restraint stress produces changes in the sleep pattern that are mainly characterized by a delayed increase in rapid eye movement sleep (REMS) amounts. Because the serotonin (5-HT) and the hypocretin (hcrt) systems that regulate REMS are interconnected, we used mutant mice deficient in the 5-HT transporter (5-HTT−/−) to examine the role of 5-HT and hcrt neurotransmissions in the sleep response to stress. In contrast to wild-type mice, restraint stress did not induce a delayed increase in REMS amounts in 5-HTT−/− mice, indicating impaired sleep homeostasis in mutants. However, pharmacological blockade of the hcrt type 1 receptor (hcrt-R1) before restraint stress restored the REMS increase in 5-HTT−/− mice. In line with this finding, 5-HTT−/− mutants displayed after restraint stress higher long-lasting activation of hypothalamic preprohcrt neurons than wild-type mice and elevated levels of the hcrt-1 peptide and the hcrt-R1 mRNA in the anterior raphe area. Thus, hypocretinergic neurotransmission was enhanced by stress in 5-HTT−/− mice. Furthermore, in 5-HTT−/− but not wild-type mice, hypothalamic levels of the 5-HT metabolite 5-hydroxyindole acetic acid significantly increased after restraint stress, indicating a marked enhancement of serotonergic neurotransmission in mutants. Altogether, our data show that increased serotonergic -and in turn hypocretinergic- neurotransmissions exert an inhibitory influence on stress-induced delayed REMS. We propose that the direct interactions between hcrt neurons in the hypothalamus and 5-HT neurons in the anterior raphe nuclei account, at least in part, for the adaptive sleep–wakefulness regulations triggered by acute stress. ER -