Modafinil

How are English bulldogs used in sleep research?

Answer: English bulldogs have been used as an animal model for obstructive sleep apnea due to their unique facial structures that makes it difficult for them to breathe while sleeping.

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Obstructive sleep apnea is a sleep disorder than can cause maintenance insomnia, a difficulty in staying asleep through the night. It is estimated that 22 million Americans experience obstructive sleep apnea on a regular basis. Sleep apnea frequently triggers waking events in the middle of the night since the person may suddenly stop breathing, so they would wake up to keep breathing. Because of sleep apnea, they may have poor sleep, which is known to correlate very closely with poor health outcomes such as depression, cardiovascular events, and type 2 diabetes. Physically, it is believed that obstructive sleep apnea occurs when the tongue collapses against the soft palate and throat, causing a blockade in the airway. It is more common in men compared to women, and obesity is a significant risk factor in sleep apnea.

The current state of treatment for obstructive sleep apnea is symptomatic. A continuous positive airway pressure (CPAP) machine forces the airway open at night when the airway is blocked, allowing a person to sleep uninterrupted. However, the actual CPAP machine can be bulky and very uncomfortable to wear, meaning there is often low compliance with treatment. Experimental treatments with indwelling stimulators can trigger a relaxation of muscles when blood oxygen gets low, which can relieve the block on the airway.

Development of an animal model for a human condition can allow scientists to test novel therapies. The English bulldog serves as a good animal model for obstructive sleep apnea because of their physiology. Like humans with sleep apnea, English bulldogs may wake frequently throughout the night, and may suffer from a lack of uninterrupted REM sleep or deep sleep.

Sleep studies involving English Bulldogs

The Hendricks lab has used the English Bulldog for developing potential new therapies for obstructive sleep apnea. One study they published in 2001 in the journal Sleep examined the effect of ondansetron, a serotonin 5-HT3 receptor antagonist, on number of waking events in a sleeping English bulldog during REM sleep. They developed a quantification of obstructive sleep events called the respiratory disturbance index. When their English bulldogs were given a placebo, they experienced 24 events per hour during REM sleep. Ondansetron decreased the number of obstructive sleep events to only 11 per hour. There was no significant improvement in the respiratory disturbance index when comparing drug treatment vs placebo during non-REM sleep, however, indicating that obstructive sleep apnea during REM sleep is serotonin dependent, while non-REM sleep is not. (The effects of ondansetron on sleep-disordered breathing in the English bulldog.)

The Hendricks lab has also studied the effect of trazodone (an antidepressant with the pharmacological action of serotonin antagonist and reuptake inhibitor) and L-tryptophan on obstructive sleep apnea. Again, using the English bulldogs as their animal model, they found that the combination of trazodone and L-tryptophan decreases the number of waking events in Non-REM sleep from 6 per hour with placebo to only 1 per hour with the drugs. Also, a similar trend is seen in REM sleep. Overall, they concluded that these drugs decrease sleep fragmentation, making sleep more consistent and reliable (The effects of trazodone with L-tryptophan on sleep-disordered breathing in the English bulldog.)

Because of these sleep related issues in the English bulldog, they may experience hypersomnolence in the daytime, just the same way humans with obstructive sleep apnea may be excessively tired in the day. Hendricks et al also tested the effects of modafinil, a daytime wakefulness drug, on these English bulldogs. Modafinil decreased total day sleep time and also increased latency to sleep, indicating that the drug can function as a wakefulness promoter in this model of hypersomnolence (Modafinil Decreases Hypersomnolence in the English Bulldog, a Natural Animal Model of Sleep-Disordered Breathing).