Discovery Under the Influence - Drugs of abuse: researchers of the University of Geneva unravel the molecular mechanism of the designer drug GHB
Professor Lüscher and his neurobiological research group have elucidated the molecular mechanism of the designer drug gamma-hydroxy butyrate (GHB) that has become increasingly popular over the last 10 years and is also know under the street names "liquid X" and "date rape drug"¹. Published today in the scientific journal Nature Neuroscience, their discovery also shows that baclofen, a substance of the same family as GHB, may be efficacious in suppressing the craving of drug abusers. The results of the research conducted at the University of Geneva shed light on a public health problem that is still poorly investigated to date.
What defines an addictive drug? What are the mechanisms underlying dependence? Why is it so difficult to quit but very easy to relapse? Interested in these questions Professor Christian Lüscher in the Dept. of Basic Neurosciences and the Clinic of Neurology of the University of Geneva and has been able to unravel the molecular mechanism of GHB. First they observed that GABAB receptors are responsible for the rewarding effects of GHB.
The reward center of the brain stem is located in a nucleus called the ventral tegmental area (VTA). It contains two types of neurons; principal cells and interneurons. Most drugs of abuse have a stimulatory effect on the VTA because their receptors are selectively found only on one of the two cell types. GABAB receptors that are the target of GHB are however located on both. Using rodent brain slices these neuroscientists have found that the interneurons are actually much more sensitive to GHB than principal cells. This explains why at lower doses GHB activates the system and causes euphoria and reward, while at higher doses the reward center is inhibited.
The elucidation of this mechanism will help to better understand the cravings that eventually lead to relapse, a key problem of addiction. Moreover it also offers an explanation as to why other compounds of same family, such as baclofen (commercially available in Switzerland under the name Lioresal) predominantly inhibit the reward circuitry and have clinically proven anti-craving properties.
¹ GHB was first synthesized in 1961 by the French researcher Henri Laborit and was initially used as an anesthetic, before becoming popular as a recreational drug. At very high doses it induces sleep that may be abused in the context of rape.
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