Ketamine administration during waking increases delta EEG intensity in rat sleep.
Ketamine is known to increase the metabolic rate of limbic brain structures. We exploited this action to test a hypothesis of the homeostatic model of delta sleep: that an increase in the waking metabolic rate of plastic neuronal systems would increase delta electroencephalographic (EEG) intensity in subsequent nonrapid-eye-movement (NREM) sleep. In separate experiments, we gave intraperitoneal injections of ketamine to Sprague-Dawley rats of either 15, 25, or 50 mg/kg (0.055, 0.091, 0.18 mmol/kg) three times, at approximately hourly intervals, during the dark (waking) period; the last dose was given 4 to 5 hours before onset of the light (sleep) period. After ketamine, both NREM duration and delta EEG intensity (amplitude and incidence) increased significantly over control (saline injections) levels. The magnitude of this increase places it among the largest pharmacologically induced stimulations of delta sleep yet observed. The interpretation of this effect is complicated by the fact that ketamine produces widespread metabolic changes throughout the brain and it also acts on several receptor classes. However, since ketamine's major action is noncompetitive blockade of the cation channel gated by the N-methyl-D-aspartate receptor, our data join recent observations that suggest that excitatory amino acid receptor systems are involved in sleep regulation.
Feinberg
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Psychiatry Service, VA Medical Center, Martinez, California.
Campbell
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D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D004576:Electromyography / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine