Physiology and Neurochemistry of Sleep Martha S. Rosenthal 1 College of Arts and Sciences, Florida Gulf Coast University, 19501 FGCU Boulevard South, Fort Myers FL 33965-6565 INTRODUCTION Human Physiology is the foundation upon which all courses related to the health professions build. Pharmacy students, in their eagerness to advance to the courses more specifi- cally related to their field, may be impatient and want to give less attention to the basic sciences. However, pharmacy students must have a solid working knowledge of the human body and the ailments that befall it before they can begin to understand the effects of pharmaceuticals. In teaching physiology to pharmacy students, it is im- portant to make the subject matter relevant to the student's lives. Finding examples which allow the students to reflect on their personal experiences is usually easy when teaching physiology. It is also important to relate subjects in physiol- ogy to other topics which are relevant to the study of pharmacy. To understand sleep, for example, the pharmacy student needs to consider concepts related to anatomy, physiology, pharmacology, pathophysiology, as well as neu- roscience. Fortunately, students have years of first-hand experience observing their own sleep behaviors and can relate this experience to the classroom experience. The following is the summary of a lecture on sleep which is usually given to pharmacy students at the end of their first year in the College of Pharmacy at the University of Florida. SLEEP Sleep is a very important drive. Studies performed on rats at the University of Chicago suggest that total sleep depriva- tion leads to death within weeks(1). Sleep is also an insistent drive; while people can deprive themselves of food and water until they die, a person cannot voluntarily sleep deprive themselves to death. Indeed, people will drift into sleep, even if they are in a situation (i.e., driving a car) in which sleeping will mean their death. It is extremely important for pharmacists to understand the basic phenomena of sleep. Many drugs have an affect on sleep, either directly (benzodiazepines, barbiturates, stimu- lants) or indirectly (opiates, melatonin). At least four of the top 10 drugs prescribed have some effect on sleep(2). BASICS OF THE SLEEP CYCLE Sleep is divided into REM Sleep and Non-REM (NREM) sleep. REM sleep (rapid eye movement) is sometimes re- ferred to as "dream sleep," although dreams can occur at any stage in the sleep cycle. NREM sleep consists of stages 1,2,3 and 4. REM and NREM stages are characterized by EEG (electroencephalogram) measurements, as well as by other physiological correlates such as the EMG (electro- 1 Assistant professor. myogram) and the EOG (electro-oculogram). The EEG measures small changes in voltage between electrodes placed on the scalp. EEG doesn't measure the discharge of a single neuron, rather it measures the summed postsynaptic potential of large portions of nervous tissue. Waves are measured for changes in duration (frequency) and in amplitude. Waves are categorized as either synchro- nized or desynchronized. Synchronized waves are high am- plitude, low frequency waves. They are seen during NREM sleep and represent a coactivation of a large number of neurons. Desynchronized waves are seen when the brain is very active (i.e., during wakefulness and REM sleep) and are low amplitude, high frequency waves. In addition to the electroencephalogram, EMG and EOG are often used in sleep labs to give information about the sleep cycle. EOG measures eye movements. During REM sleep, you can observe the rapid eye movements that give REM sleep its name. EMG measures muscle activity. It is highest during wakefulness, lower during NREM sleep, and, except for occasional twitches, flat during REM sleep, as muscle atonia occurs during REM sleep. Muscle atonia is a characteristic of REM sleep that has been utilized by sleep researchers in order to preferentially deprive lab animals of REM sleep. The "flowerpot" technique involves placing an animal (i.e., a rat) on top of an upside down flower pot in a bucket of water. The rat has ample room when he is awake, and can enter NREM sleep, but as soon as he enters REM sleep, he loses muscle tone, falls off the flowerpot, and splashes down into the bucket of water. He soggily and grumpily climbs back up onto his flowerpot, and goes back into NREM sleep. During the next entry into REM sleep, he's back in the water. Thus he is preferentially deprived of REM sleep. SLEEP CYCLE Sleep is divided into a 90 minute cycle of NREM sleep and REM sleep. This cycle is repeated 3-6 times during the night. Generally, a night of sleep begins with about 80 minutes of NREM and 10 minutes of REM sleep. As the sleep cycle progresses through the night there is less stage 3,4 NREM sleep and more REM sleep. Thus, there is more REM sleep on towards morning, which explains why when you awaken in the morning, you generally awaken from a dream. Wakefulness. There are two main types of EEG waves during wakefulness. Beta waves are desynchronized; low voltage (low amplitude), and of a high-mixed frequency. They are seen when the patient is alert and engaged. Alpha waves are low voltage, mixed frequency waves, and are more synchronous than beta waves. They are seen when then subject is relaxed or drowsy, with their eyes closed. 204 American Journal of Pharmaceutical Education Vol. 62, Summer 1998