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Noradrenaline, one of the main brain monoamines, has powerful central influences on forebrain neurobiological processes which support the mental activities occurring during the sleep-waking cycle. Noradrenergic neurons are activated during waking, decrease their firing rate during slow wave sleep, and become silent during rapid eye movement (REM) sleep. Although a low level of noradrenaline is still maintained during REM sleep because of diffuse extrasynaptic release without rapid withdrawal, the decrease observed during REM sleep contributes to the mentation disturbances that occur during dreaming, which principally resemble symptoms of schizophrenia but seemingly also of attention deficit hyperactivity disorder.

Although the main peripheral features of dreaming were identified two millennia ago, the neurobiological study of the basic and higher integrated processes underlying rapid eye movement (REM) sleep only began about 70 years ago. Today, the combined contributions of the successive and complementary methods of electrophysiology, imaging, pharmacology, and neurochemistry have provided a good level of knowledge of the opposite but complementary activating and inhibitory processes which regulate waking mentation and which are disturbed during REM sleep, inducing a schizophrenic-like mental activity., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Sigmund Freud's thesis was that there is a censorship during waking that prevents memory of events, drives, wishes, and feelings from entering the consciousness because they would induce anxiety due to their emotional or ethical unacceptability. During dreaming, because the efficiency of censorship is decreased, latent thought contents can, after dream-work involving condensation and displacement, enter the dreamer's consciousness under the figurative form of manifest content. The quasi-closed dogma of psychoanalytic theory as related to unconscious processes is beginning to find neurobiological confirmation during waking. Indeed, there are active processes that suppress (repress) unwanted memories from entering consciousness. In contrast, it is more difficult to find neurobiological evidence supporting an organized dream-work that would induce meaningful symbolic content, since dream mentation most often only shows psychotic-like activities., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Animal models are a promising method to approach the basic mechanisms of the neurobiological disturbances encountered in mental disorders. Depression is characterized by a decrease of REM sleep latency and an increase of rapid eye movement density. In schizophrenia, electrophysiological, tomographic, pharmacological and neurochemical activities are all encountered during REM sleep. Mental retardation and dementia are characterized by rather specific REM sleep disturbances. Identification of the genetic support for these abnormalities (endophenotypes) encountered during REM sleep could help to develop specific treatments.

This study tested the influence of CGP 36742, a both gamma-aminobutyric acid(B) (GABA(B)) and GABA(C) receptor antagonist, on sleep and waking. The compound was injected intraperitoneally at 1, 10, 30, 100, 300 and 500 mg/kg to rats which were recorded during 6 h. Only at 500 mg/kg, total waking was increased during third and fourth hours and total duration of recording by a specific enhancement of quiet waking (without hippocampal theta activity). Slow wave sleep was decreased at 100, 300, 500 mg/kg during the third and fourth hours, and during total recording time at 500 mg/kg. Paradoxical sleep was not affected. While it was not possible to distinguish already known GABA(B) and GABA(C) identical influence on waking and slow wave sleep, their previously shown opposite effect on paradoxical sleep seemed to nullify each other.

Normal waking mentation is the outcome of the combined action of both electrophysiological and neurochemical antagonistic and complementary activating and inhibitory influences occurring mainly in the cerebral cortex. The chemical ones are supported principally by acetylcholine, and noradrenaline and serotonin, respectively. During rapid eye movement (REM) sleep, the monoaminergic silence - except dopaminergic ongoing activity - disrupts this equilibrium and seems to be responsible for disturbances of mental activity characteristic of dreaming. This imbalance could cause disconnectivity of cortical areas, failure of latent inhibition and possibly the concomitant prefrontal dorsolateral deactivation. Moreover, the decrease of prefrontal dopaminergic functioning could explain the loss of reflectiveness in this sleep stage. All these phenomena are also encountered in schizophrenia. The psychotic-like mentation of dreaming (hallucinations, delusions, bizarre thought processes) could result from the disinhibition of dopamine influence in the nucleus accumbens by the noradrenergic and serotonergic local silence and/or the lifting of glutamate influence from the prefrontal cortex and hippocampus. We hypothesize that, during REM sleep, the increase of dopamine and the decrease of glutamate release observed in nucleus accumbens reach the threshold values at which psychotic disturbances arise during wakefulness. Whatever the precise mechanism, it seems that the functional state of the prefrontal cortex and nucleus accumbens is the same during dreaming sleep stage and in schizophrenia. The convergent psychological, electrophysiological, tomographic, pharmacological and neurochemical criteria of REM sleep and schizophrenia suggest that this sleep stage could become a good neurobiological model of this psychiatric disease.

Brain function is supported by central activating processes that are significant during waking, decrease during slow wave sleep following waking and increase again during paradoxical sleep during which brain activation is as high as, or higher than, during waking in nearly all structures. However, inhibitory mechanisms are crucial for sleep onset. They were first identified by behavioral, neuroanatomical and electrophysiological criteria, then by pharmacological and neurochemical ones. During slow wave sleep, they are supported by GABAergic mechanisms located at midbrain, mesopontine and pontine levels but are induced and sustained by forebrain and hindbrain influences. GABAergic processes are also responsible for paradoxical sleep occurrence, particularly by suppression of noradrenaline and serotonin (5-HT) inhibition of paradoxical sleep-generating structures. Hindbrain and forebrain modulate these structures situated at the mesopontine level. For sleep mentation, the noradrenergic and serotonergic silence is thought, today, to be directly, or indirectly, responsible for dopamine predominance and glutamate decrease in the nucleus accumbens, which could be the background of the well-known psychotic-like mental activity of dreaming.