This study will examine whether various drugs affecting sleep cycles can improve different kinds of memory.

Research provides evidence for strong, specific connections between sleeping and memory. This research shows that sleeping is necessary for certain types of memories to form, certain sleep stages lead to specific types of learning and memory consolidation, and naps are as effective as night-time sleep in these learning and memory processes. Current evidence also indicates that there are different types of memory and that the different types can operate and develop independently. In this study, three different memory types will be examined: perceptual, motor, and declarative memory. Perceptual memory is measured through the ability to recognize discrete stimuli; motor memory is measured through the ability to perform specific, coordinated tasks; and declarative memory is measured through the ability to recite memorized information. Different stages in the sleep cycle correlate with improvements in each of these memory processes. For instance, improvement of perceptual memory tasks is dependent on rapid eye motion (REM) sleep; motor learning is related to sleep stage 2; and declarative memory consolidation is related to short wave sleep (SWS), which includes sleep stages 3 and 4.

New drugs can target specific sleep stages and increase the amount of time people spend in those stages when they sleep. For example, the new prescription drug zolpidem increases time spent in stage 2 during sleep, and the drug sodium oxybate increases time spent in SWS. Compared to sleep impacted by either zolpidem or sodium oxybate, normal sleep has proportionally more time spent in REM. This study will use medications, or their lack, to manipulate how much time is spent in REM, stage 2, and SWS. The study will then examine whether the percentage of sleep spent in different stages affects the learning processes associated with those stages.

Participation in this study will last 6 weeks. At the outset, participants will undergo a 2-hour screening visit that will include a medical history, a physical examination, routine lab tests, urine tests for drugs and pregnancy, an electrocardiogram, and a clinical interview for mental health. Participants will also be asked to complete a series of questionnaires on subjective sleep quality, sleep quantity, and daytime sleepiness.

Participants will complete five study visits, beginning 1 week from screening and separated by 5 to 10 days to allow drug wash-out and recovery from effects of the previous visit. Each study visit will involve an overnight stay in a sleep lab. Participants will arrive at 8 PM, go to bed at 10 PM, and be awakened at 5 AM. Between 6 and 8 AM, they will undergo three different tests, each corresponding to a different type of learning and memory process: perceptual, motor, or declarative. The test will include recognizing a target image, typing a specific finger sequence on a keyboard, and verbally recalling a list of words. Participants will receive one of the study drugs or placebo at 8:30 AM and then be allowed to take a 90-minute nap between 9 and 11 AM. They will receive a different drug, different dosage, or placebo at each study visit. Between 4 and 6 PM, they will be retested on the previous three tests. While sleeping, participants will be outfitted with sensors monitoring muscle activity, eye movements, brain waves, heart and lung functioning, and—on the first night—breathing.

For the entire duration of the study, participants will wear an actigraph, which is a wristwatch-like device that monitors sleep cycles. Participants will also be required to maintain a regular sleep schedule, going to sleep and waking up in the same 2-hour window each day. They will also report on sleep schedule and caffeine, alcohol, and drug use in a daily sleep diary. Caffeine, alcohol, and drug use will be prohibited starting at noon on the day prior to each study visit.

• Drug: Low-dose sodium oxybate
• Drug: High-dose sodium oxybate
• Drug: Low-dose zolpidem
• Drug: High-dose zolpidem
• Drug: Placebo

Inclusion Criteria:

• Speaks English
• Resides in the general San Diego community
• Completed at least 12 years of formal education, because education may affect performance on the cognitive task

Exclusion Criteria:

• No regular sleep-wake schedule, defined as not meeting study criteria or scoring between 31 and 69 on the Horne-Ostberg Morningness-Eveningness Questionnaire
• Presence of a sleep disorder reported or detected on the questionnaires
• Personal or immediate family (i.e., first degree relative) history of diagnosed significant psychopathology
• Personal history of head injury with loss of consciousness for more than 15 minutes or with seizures
• History of substance dependence
• Current use of any psychotropic medications
• Any cardiac, respiratory, or other medical condition that may affect cerebral metabolism
• Noncorrectable vision and audition impairments