INTRODUCTION BASIC RESEARCH IN SLEEP AND ANESTHESIA AIMS TO UNDERSTAND THE BRAIN MECHANISMS GENERATING STATES OF CONSCIOUSNESS AND STATE-DEPENDENT ALTER- ATIONS IN AUTONOMIC CONTROL.1 Neural systems

BASIC RESEARCH IN SLEEP AND ANESTHESIA AIMS TO UNDERSTAND THE BRAIN MECHANISMS GENERATING STATES OF CONSCIOUSNESS AND STATE-DEPENDENT ALTERATIONS IN AUTONOMIC CONTROL.1 Neural systems that evolved to generate natural sleep are postulated to be preferentially involved in mediating anesthetically induced losses of waking consciousness.2 Neurotransmitter-receptor systems known to be important for both sleep and anesthesia include glutamate and N-methyl-D-aspartate (NMDA) receptors3,4 and acetylcholine (ACh) and muscarinic receptors.5,6 An interaction between these two neurotransmitter systems is the focus of the present report. NMDA receptor-coupled ion channels are blocked by the commonly used anesthetic ketamine. First introduced into clinical practice7 in 1965, ketamine is referred to as a dissociative anesthetic because it can produce analgesia and amnesia without causing a loss of consciousness.3 NMDA receptor blockers modulate sleep and wakefulness4,8 and microinjection of NMDA into rat basal forebrain enhances wakefulness and depresses slow wave sleep.9 Acetylcholinesterase inhibitors are used frequently in anesthesia to reverse the actions of sedative/hypnotic drugs, and new studies show that physostigmine reverses unconsciousness caused by the intravenously administered anesthetic propofol.10 Acetylcholine (ACh) also is known to contribute to sleep-cycle control by its actions in the medial pontine reticular formation (mPRF). Ketamine decreases ACh turnover in some brain regions11 and ketamine anesthesia can be antagonized by acetylcholinesterase inhibitors.12 No previous studies have described the effect of NMDA antagonists on pontine cholinergic neurotransmission. Therefore, the present study examined the hypothesis that ketamine and the NMDA-channel blocker dizocilpine maleate (MK-801) would decrease ACh release in the mPRF.