title: cis-3-Hexenol and trans-2-hexenal mixture prevents development of PTSD-like phenotype in rats.
abstract: Several green leaf volatiles have anxiolytic/antidepressant properties and attenuate adrenocortical stress response in rodents. However, it remains unknown whether a mixture of cis-3-hexenol and trans-2-hexenal so-called 'green odor (GO)' affects fear-associated post-traumatic stress disorder (PTSD)-like behavior. In the present study, fear memory of the initial conditioning stimulus was stably maintained by weekly presentation of conditioned tone. Examination of open field behavior, acoustic startle response, prepulse inhibition, and immobility in the forced swim test for 2 weeks after initial conditioning revealed that conditioned rats sustained anxiety, enhanced startle response, hypervigilance, depression-like behavior, and hypocortisolism, which is consistent with PTSD symptoms. Daily, not acute, GO presentation facilitated fear extinction and reduced PTSD-like behavioral and endocrinal responses. To further investigate the mechanism of effect of GO, we examined the effect of paroxetine (a selective serotonin reuptake inhibitor), p-chlorophenylalanine (PCPA, an irreversible serotonin synthesis inhibitor), alone or in combination of GO on PTSD-like phenotype. The alleviative effects of GO were masked by simultaneous paroxetine administration. PCPA-induced serotonin depletion abolished the effects of GO. Our results suggest that daily GO presentation facilitates fear extinction and prevents development of PTSD-like symptoms.
authors.affiliation: Hirosaki University Graduate School of Medicine, Hirosaki, Japan; Department of Neurophysiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nikaido
authors.affiliation: Department of Neurophysiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; Department of Biomedical Sciences, Division Sciences, Hirosaki, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Yamada
authors.affiliation: Department of Neurophysiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; Medicinal Informatics and Research Unit, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Migita
authors.affiliation: Department of Neurophysiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shiba
authors.affiliation: Department of Neurophysiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nakashima
authors.affiliation: Department of Neurophysiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. Electronic address: shinyau@hirosaki-u.ac.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ueno
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005106:Exploratory Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D010134:Fenclonine / Q000494:pharmacology; D000441:Hexanols / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017374:Paroxetine / Q000494:pharmacology; D010641:Phenotype; D065808:Prepulse Inhibition / Q000187:drug effects; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D000447:Aldehydes; D000441:Hexanols; D011619:Psychotropic Drugs; C051918:3-hexen-1-ol; D017374:Paroxetine; C051750:2-hexenal; D010134:Fenclonine
keywords: Paroxetine; Post-traumatic stress disorder (PTSD); cis-3-Hexenol; p-Chlorophenylalanine; trans-2-Hexenal