Biomedical subjects

Claude Gottesmann

Publications and source records attributed to Claude Gottesmann.

5 recordsLinked to original sources

PubMed2006

Influence of a GABA(B) and GABA(C) receptor antagonist on sleep-waking cycle in the rat.

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.

Analysis of Variance↗

PubMed2006

[Dreaming and schizophrenia: a common neurobiological background?].

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.

Animals↗

PubMed2004

Brain inhibitory mechanisms involved in basic and higher integrated sleep processes.

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.

Animals↗

PubMed2002

GABA mechanisms and sleep.

GABA is the main inhibitory neurotransmitter of the CNS. It is well established that activation of GABA(A) receptors favors sleep. Three generations of hypnotics are based on these GABA(A) receptor-mediated inhibitory processes. The first and second generation of hypnotics (barbiturates and benzodiazepines respectively) decrease waking, increase slow-wave sleep and enhance the intermediate stage situated between slow-wave sleep and paradoxical sleep, at the expense of this last sleep stage. The third generation of hypnotics (imidazopyridines and cyclopyrrolones) act similarly on waking and slow-wave sleep but the slight decrease of paradoxical sleep during the first hours does not result from an increase of the intermediate stage. It has been shown that GABA(B) receptor antagonists increase brain-activated behavioral states (waking and paradoxical sleep: dreaming stage). Recently, a specific GABA(C) receptor antagonist was synthesized and found by i.c.v. infusion to increase waking at the expense of slow-wave sleep and paradoxical sleep. Since the sensitivity of GABA(C) receptors for GABA is higher than that of GABA(A) and GABA(B) receptors, GABA(C) receptor agonists and antagonists, when available for clinical practice, could open up a new era for therapy of troubles such as insomnia, epilepsy and narcolepsy. They could possibly act at lower doses, with fewer side effects than currently used drugs. This paper reviews the influence of different kinds of molecules that affect sleep and waking by acting on GABA receptors.

Animals↗

PubMed2002

The neurochemistry of waking and sleeping mental activity: the disinhibition-dopamine hypothesis.

This paper describes a hypothesis related to the neurochemical background of sleep-waking mental activity which, although associated with subcortical structures, is principally generated in the cerebral cortex. Acetylcholine, which mainly activates cortical neurons, is released at the maximal rate during waking and rapid eye movement (REM) sleep dreaming stage. Its importance in mental functioning is well-known. However, brainstem-generated monoamines, which mainly inhibit cortical neurons, are released during waking. Both kinds of influences contribute to the organized mentation of waking. During slow wave sleep, these two types of influence decrease in intensity but maintain a sufficiently high level to allow mental activity involving fairly abstract pseudo-thoughts, a mode of activity modelled on the diurnal pattern of which it is a poor reply. During REM sleep, the monoaminergic neurons become silent except for the dopaminergic ones. This results in a large disinhibition and the maintained dopamine influence may be involved in the familiar psychotic-like mental activity of dreaming. Indeed, in this original activation-disinhibition state, the increase of dopamine influence at the prefrontal cortex level could explain the almost total absence of negative symptoms of schizophrenia during dreaming, while an increase in the nucleus accumbens is possibly responsible for hallucinations and delusions, which are regular features of mentation during this sleep stage.

Acetylcholine↗