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Paris, December 15, 2003

The psychological and behavioral effects of GHB or the "date rape drug" on the thalamus

Nathalie Leresche, research director at the CNRS and her colleagues at the Laboratoire de Neurobiologie des Processus Adaptatifs (CNRS-Université Paris 6), in partnership with Vincenzo Crunelli's team (Cardiff University, UK), studied the effects of gamma-hydroxybutyric acid [1] or GHB, better known to the general public as the "date rape drug", on a key region of the nervous system involved in sleep: the thalamus. This was the first time that research made it possible to link the effects of GHB at the cellular level to its behavioral effects. This study was conducted within the framework of the international research program launched in 2001 by the National Institute of Drug Abuse (NIDA-National Institute of Health, USA) as a result of the increased illegal consumption of GHB. Published on December 10, 2003, in the review Journal of Neuroscience, this research was financed by the NIDA and the Mission Interministérielle de Lutte Contre la Drogue et la Toxicomanie.

Despite its many well-known neurological effects (hypnotic properties, euphoric and disinhibiting effects, etc.), the action mechanism of GHB on neurons in the central nervous system is still poorly understood although GHB is naturally present in the brain at very low concentrations.  For example, GHB targets and the type of receptors that recognize this molecule are still in debate and the effects of GHB on the excitability of neurons and the neuronal network remain relatively unclear.  This research, which characterizes the effects of GHB at the thalamic level, contributes to the understanding of the effects of this drug on sleep.    

 

Neurons in the thalamus region are subject to rhythmic oscillating electrical activity during deep sleep stages.  This characteristic behavior can be modified by releasing molecules such as gamma-aminobutyric acid (GABA) and glutamate, which are the main neurotransmitters of inhibition and excitation, respectively, in the central nervous system.  These researchers showed that GHB specifically activates a type of GABA receptor known as GABA-B.  Different mechanisms are triggered, depending on the doses administered. 

 

 

At low doses (250µM in the cephalorachidian liquid), GHB acts at the level of the synapses that contact the neurons of the thalamus and leads to an imbalance in the ratio between the excitation and inhibition information received by the neurons.  This imbalance results in pathological rhythmic activities identical to those observed during nonconvulsive epilepsy seizures, of the "absence" type, which are characterized by losses of consciousness.  This form of epilepsy was observed in monkeys when they were given low doses of GHB. 

 

At higher doses, corresponding to concentrations associated with hypnotic effects, GHB reduces the release of glutamate and GABA, leading to a decrease in the amount of information received by the thalamic neurons.  Moreover, at these concentrations, GHB directly acts on the neurons that develop during the oscillating activity characteristic of deep sleep stages. 

 

Therefore, the hypnotic effect of GHB as well as its capacity to regulate sleep rhythms and to induce some types of epilepsy can be explained, in large part, by its action on the activity of thalamic neuronal networks. 

Notes:

1 In 1964, Henri Laborit synthesized a new compound, gamma-hydroxybutyric acid or GHB, that turned out to have hypnotic properties. As a result of this observation, GHB was clinically used as an anesthetic and then, more recently, in the treatment of narcolepsy, a pathology of sleep rhythms. Until the time it was officially included on the list of narcotics in 1999, GHB was sold over the counter. However, the simplicity of the chemical structure of this molecule that is produced by the metabolism of gamma-aminobutyric acid (GABA) makes it easy to synthesize and provides a readily available source. Excessive consumption of GHB, aside from its being illegal, has acute toxicity risks. The ingestion of high doses of GHB leads to respiratory depression that can induce a coma. Moreover, the repeated use of GHB creates a dependence that may result in prolonged and severe addiction.

2 GHB was adopted by bodybuilders to develop muscle mass as a result of its effect on the endogenous release of growth hormone. Illegal uses of GHB have emerged since the beginning of the 1990's. Basically, at very low doses, GHB has euphoric and disinhibiting effects that have led to its use as a "recreational drug". In this context, GHB is often referred to as "liquid ecstasy". At the same time, higher doses of GHB administered illegally induce a type of hypnosis associated with amnesia. This use, particularly concerning rape cases, has led the media to coin GHB as the "date rape drug".

Contacts:

Researcher contact:
Nathalie Leresche
Laboratoire de Neurobiologie des Processus Adaptatifs (CNRS-Université Paris 6)
Tel: +33 1 44 27 25 85
E-mail: Nathalie.Leresche@snv.jussieu.fr

Press contact:
Laëtitia Louis
Tel: +33 1 44 96 49 88
E-mail: Laetitia.louis@cnrs-dir.fr

Life Sciences Department contact:
Françoise Tristani
Tel: +33 1 44 96 40 26


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