Four weeks later, they were injected intraperitoneally with a designer receptors exclusively activated by designer drug (DREADD) agonist (compound 21) at 3 mg/kg in 90 l or 90 l 0

Four weeks later, they were injected intraperitoneally with a designer receptors exclusively activated by designer drug (DREADD) agonist (compound 21) at 3 mg/kg in 90 l or 90 l 0.2% DMSO in normal saline (vehicle), solvent for compound 21, 30 min before the one-hour conversation between familiar observers and mice with surgery. surgery mice before the surgery. Familiar observers developed anxious behavior after being with surgery mice. Surgery mice with familiar observers had less anxious behavior than surgery mice without interacting with familiar observers. Multiple brain regions including paraventricular thalamic nucleus (PVT) were activated in familiar observers. The activated cells in PVT contained orexin receptors. Injuring the neurons with ibotenic acid, antagonizing orexin signaling with an anti-orexin antibody or inhibiting neurons by chemogenetic approach in PVT abolished the consolation and anxious behaviors of familiar observers. Conclusions: Mice show consolation behavior toward the sick. This Linalool behavior attenuates the anxious behavior of surgery mice. The orexin signaling in the PVT neurons play a critical role in the consolation of familiar observers toward surgery mice and their anxious behavior. Considering that about 50 million patients have medical procedures annually in the United States, our study represents the initial attempt to understand neural mechanisms for consolation and stress of a large number of people. strong class=”kwd-title” Keywords: anxious behavior, consolation behavior, mice, orexin, paraventricular thalamic nucleus, surgery. Introduction Consolation behaviors toward the sick are a common presentation in humans and an important component of empathetic responses. These behaviors include giving a hug or gentle touching to the sick in humans 1. About 50 million patients have medical procedures each year in the United States 2. Relatives, friends or even strangers often show consolation behavior toward these patients. Various forms of empathy, such as targeted helping and mirroring, have been shown in non-human primates and elephants, animals with advanced cognitive capacities 3. Empathy for pain and toward distressed others as well as contagious itch behavior have been shown in mice 4-6. The distress stimuli include pain induced by various etiologies and interpersonal defeat 6-9. However, small animal model of consolation behavior toward Linalool the sick has not been established and the neural mechanisms for this behavior are not known. Patients and their relatives are often anxious when they have medical procedures. Anxiety is known to cause physiological responses and worsen outcome of patients with various diseases 10-12. It is known that caregiving spouses of patients with dementia have an increased chance to suffer from dementia 13. The mechanism for this phenomenon is not clear. However, factors, such as increased stress and comparable living environment, may contribute to the development of dementia in the caregiving spouses 13, 14. These findings suggest that stress of the relatives of surgical patients can have significant adverse effects on the health of surgical patients’ relatives. However, no animal model simulating this stress has been reported and the neural and molecular mechanisms for this behavior have not been explored. This study was aimed at determining whether FGD4 small animals, such as mice, had consolation behavior toward surgical mice and developed anxious behavior after interacting with surgical mice and defining neural mechanisms for these behaviors. Methods and Materials Linalool The animal protocol was approved by the Institutional Animal Care and Use Committee of the University of Virginia (Charlottesville, VA, USA). All animal experiments were carried out in accordance with the National Institutes of Health Guideline for the Care and Use of Laboratory Animals (NIH publications number 80-23) revised in 2011 and reported according to the Appear guidelines. Animals and animal groups Six- to 8-week aged CD-1 male mice (weighing 31 – 36 g) from Charles River Laboratories International Inc. (Wilmington, MA, USA) were used because this age of mice had consistent learning and memory impairment with 100% survival rate after surgery in our previous study 15. The mice were housed in cages (5 mice/cage) on a 12-h light/dark cycle with free access to water and food. All experimental procedures or behavior assessments were conducted during the light phase. In the first experiment (Physique ?(Figure1A),1A), three individual cohorts of mice were used. In the first cohort, mice were randomized by a SPSS-generated random number assignment to one of five groups: control, surgery, familiar observer, separated observer and unfamiliar observer. Control mice lived together with other control mice (5 mice per cage that was 26 x 15 x 12 cm) and were not exposed to surgery mice or unfamiliar intruders. Surgery mice had medical procedures under anesthesia with 1.8% isoflurane for 2 h. Familiar observers were cage-mates of surgery mice prior to their surgery for at least 2 weeks..