title: The wake-promoting drug modafinil stimulates specific hypothalamic circuits to promote adaptive stress responses in an animal model of PTSD.
abstract: Pharmacotherapeutic intervention during traumatic memory consolidation has been suggested to alleviate or even prevent the development of posttraumatic stress disorder (PTSD). We recently reported that, in a controlled, prospective animal model, depriving rats of sleep following stress exposure prevents the development of a PTSD-like phenotype. Here, we report that administering the wake-promoting drug modafinil to rats in the aftermath of a stressogenic experience has a similar prophylactic effect, as it significantly reduces the prevalence of PTSD-like phenotype. Moreover, we show that the therapeutic value of modafinil appears to stem from its ability to stimulate a specific circuit within the hypothalamus, which ties together the neuropeptide Y, the orexin system and the HPA axis, to promote adaptive stress responses. The study not only confirms the value of sleep prevention and identifies the mechanism of action of a potential prophylactic treatment after traumatic exposure, but also contributes to understanding mechanisms underlying the shift towards adaptive behavioral response.
authors.affiliation: Anxiety and Stress Research Unit, Beer-Sheva Mental Health Center, Ministry of Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.|Department of Psychology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Cohen
authors.affiliation: Headache Clinic, Department of Neurology, Soroka Medical Centre, Ben-Gurion University of the Negev, Beer- Sheva, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Ifergane
authors.affiliation: Anxiety and Stress Research Unit, Beer-Sheva Mental Health Center, Ministry of Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Vainer
authors.affiliation: Anxiety and Stress Research Unit, Beer-Sheva Mental Health Center, Ministry of Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: M A
authors.initials: MA
authors.lastname: Matar
authors.affiliation: Anxiety and Stress Research Unit, Beer-Sheva Mental Health Center, Ministry of Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Z
authors.initials: Z
authors.lastname: Kaplan
authors.affiliation: Division of Psychiatry, The Chaim Sheba Medical Center, Ramat-Gan, Israel.|Sackler Medical School, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: J
authors.initials: J
authors.lastname: Zohar
authors.affiliation: Karolinska Institutet - Clinical Neuroscience, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: A A
authors.initials: AA
authors.lastname: Mathé
authors.affiliation: Anxiety and Stress Research Unit, Beer-Sheva Mental Health Center, Ministry of Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.|Department of Psychology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: H
authors.initials: H
authors.lastname: Cohen
mesh_terms: D000223:Adaptation, Psychological / Q000187:drug effects*; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D007031:Hypothalamus / Q000187:drug effects*; D008297:Male; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D000077408:Modafinil; D009415:Nerve Net / Q000187:drug effects*; D009478:Neuropeptide Y / Q000502:physiology; D000068797:Orexins / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013313:Stress Disorders, Post-Traumatic / Q000517:prevention & control* / Q000523:psychology*; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D001559:Benzhydryl Compounds; D009478:Neuropeptide Y; D000068797:Orexins; D000077408:Modafinil; D003345:Corticosterone