Identification of MK-8133: An orexin-2 selective receptor antagonist with favorable development properties.

Antagonism of orexin receptors has shown clinical efficacy as a novel paradigm for the treatment of insomnia and related disorders. Herein, molecules related to the dual orexin receptor antagonist filorexant were transformed into compounds that were selective for the OX2R subtype. Judicious selection of the substituents on the pyridine ring and benzamide groups led to 6b; which was highly potent, OX2R selective, and exhibited excellent development properties.

Artificial light at night disrupts sleep in female great tits (Parus major) during the nestling period, and is followed by a sleep rebound.

Artificial light at night has been linked to a wide variety of physiological and behavioural consequences in humans and animals. Given that little is known about the impact of light pollution on sleep in wild animals, we tested how experimentally elevated light levels affected sleep behaviour of female songbirds rearing 10 day old chicks. Using a within-subject design, individual sleep behaviour was observed over three consecutive nights in great tits (Parus major), with females sleeping in a natural dark situation on the first and third night, whereas on the second night they were exposed to a light-emitting diode (1.6 lux). Artificial light in the nest box dramatically and significantly affected sleep behaviour, causing females to fall asleep later (95 min; while entry time was unaffected), wake up earlier (74 min) and sleep less (56%). Females spent a greater proportion of the night awake and the frequency of their sleep bouts decreased, while the length of their sleep bouts remained equal. Artificial light also increased begging of chicks at night, which may have contributed to the sleep disruption in females or vice versa. The night following the light treatment, females slept 25% more compared to the first night, which was mainly achieved by increasing the frequency of sleep bouts. Although there was a consistent pattern in how artificial light affected sleep, there was also large among-individual variation in how strongly females were affected. When comparing current results with a similar experiment during winter, our results highlight differences in effects between seasons and underscore the importance of studying light pollution during different seasons. Our study shows that light pollution may have a significant impact on sleep behaviour in free-living animals during the reproductive season, which may provide a potential mechanism by which artificial light affects fitness.

Clinical signs and management of anxiety, sleeplessness, and cognitive dysfunction in the senior pet.

Physical signs of old age may be obvious, but mental and cognitive changes require more careful observation. Changes in behavior may represent the earliest indications of medical problems, or disorders of the central nervous system, and these may be bidirectional. Cognitive dysfunction syndrome is underdiagnosed and affects a substantial portion of aged companion animals. This article describes potential treatment regimens to address age-related behavioral problems, as well as a framework for investigating differential diagnoses. Early identification of changes in behavior is essential for the adequate treatment and management of medical and behavioral problems, and for monitoring outcomes.

Melatonina, triptófano y sus efectos sobre el envejecimiento, sistema inmune y sueño en animales de hábitos diurnos (Streptopelia risoria) / Melatonin, tryptophan and their effects on aging, immune system and sleepin animals with diurnal habits (Streptopelia Risoria)

Aunque el envejecimiento es un proceso multifactorial, los descensos en los niveles de melatonina y serotonina observados en el anciano son, probablemente, factores relevantes. Las consecuencias directas de estos descensos determinan dificultad en conciliar el sueño, perturbaciones en los ritmos circadianos, además de otros trastornos debidos a la reducción en la protección antioxidante y depresión de la función inmune. Existen numerosos estudios que indican la existencia de una estrecha relación entre la pérdida del ritmo circadiano de melatonina y los cambios relacionados con la edad en los ritmos de actividad-reposo. Considerando que la melatonina determina la organización temporal del organismo, esta hormona, bien administrada directamente o facilitando su síntesis por la aportación de su precursor, el triptófano, podría ser un importante agente para el tratamiento de las perturbaciones relacionadas con la edad en la organización circadiana, el sueño y el resto de desórdenes que acompañan a la vejez para contrarrestar lo que ha venido denominándose “estado deficiente en melatonina”, que típicamente aparece en la edad avanzada. Los resultados obtenidos por nuestro grupo de investigación en la tórtola collariza (Streptopelia risoria), una especie cuyas características circadianas son similares a las del ser humano, apoyan esta propuesta (AU)

Although aging is a multifactorial process, the age-related decline in melatonin and serotonin secretion seems to be a relevant factor. The direct consequences of their loss with age are related to problems in the capacity to achieve sleep and perturbations of the circadian rhythm, as well as other related disorders such as a lessened antioxidant protection and a depressed immune function. An ever growing body of research indicates the existence of a close relationship between the 24-hour melatonin rhythm and age-related changes in the physiology of the activity-rest rhythms. Considering that melatonin acts by sending the organism information on its temporal organization, this hormone, either directly or through its creation by the conversion of its precursor, the amino acid tryptophan, could be an important pharmacological agent to attenuate age-related changes in circadian organization, sleep, and other disorders that accompany aging to counteract what has been called the “melatonin deficient state” that typically appears in old age. The findings obtained by our research group in the ring dove (Streptopelia risoria), a species with activity-rest cycles similar to those of human beings, that have been summarized in the present review support this proposal (AU)