GHB: Difference between revisions

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However, at therapeutic doses, GHB reaches much higher concentrations in the brain and activates [[GABA]]B receptors, which are primarily responsible for its sedative effects.<ref>Drosophila GABAB receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB) | http://www.sciencedirect.com/science/article/pii/S0014299905007442</ref> GHB's sedative effects are blocked by GABAB [[antagonists]].

The role of the GHB receptor in the behavioural effects induced by GHB is more complex. GHB receptors are densely expressed in many areas of the brain, including the cortex and hippocampus, and these are the receptors that GHB displays the highest affinity for. There has been somewhat limited research into the GHB receptor; however, there is evidence that activation of the GHB receptor in some brain areas results in the release of glutamate, the principal excitatory neurotransmitter.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref> Drugs that selectively activate the GHB receptor cause absence seizures in high doses, as do GHB and [[GABA]]B agonists.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref>

There has been somewhat limited research into the GHB receptor; however, there is evidence that activation of the GHB receptor in some brain areas results in the release of [[glutamate]], the principal excitatory neurotransmitter.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref> Drugs that selectively activate the GHB receptor cause absence seizures in high doses, as do GHB and [[GABA]]B agonists.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref>

Activation of both the GHB receptor and [[GABA]]B is responsible for the addictive profile of GHB. GHB's effect on dopamine release is biphasic.<ref>Drosophila [[GABA]]B receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB) | http://www.sciencedirect.com/science/article/pii/S0014299905007442</ref> Low concentrations stimulate dopamine release via the GHB receptor.<ref>A specific gamma-hydroxybutyrate receptor ligand possesses both antagonistic and anticonvulsant properties | http://www.ncbi.nlm.nih.gov/pubmed/2173754</ref> Higher concentrations inhibit dopamine release via [[GABA]]B receptors as do other [[GABA]]B [[agonists]] such as [[baclofen]] and [[phenibut]].<ref>Tonic GABA-ergic modulation of striatal dopamine release studied by in vivo microdialysis in the freely moving rat | http://www.sciencedirect.com/science/article/pii/001429999500369V</ref> After an initial phase of inhibition, [[dopamine]] release is then increased via the GHB receptor.

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 However, at therapeutic doses, GHB reaches much higher concentrations in the brain and activates [[GABA]]<sub>B</sub> receptors, which are primarily responsible for its sedative effects.<ref>Drosophila GABAB receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB) | http://www.sciencedirect.com/science/article/pii/S0014299905007442</ref> GHB's sedative effects are blocked by GABA<sub>B</sub> [[antagonists]].
-The role of the GHB receptor in the behavioural effects induced by GHB is more complex. GHB receptors are densely expressed in many areas of the brain, including the cortex and hippocampus, and these are the receptors that GHB displays the highest affinity for. There has been somewhat limited research into the GHB receptor; however, there is evidence that activation of the GHB receptor in some brain areas results in the release of glutamate, the principal excitatory neurotransmitter.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref> Drugs that selectively activate the GHB receptor cause absence seizures in high doses, as do GHB and [[GABA]]<sub>B</sub> agonists.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref>
+There has been somewhat limited research into the GHB receptor; however, there is evidence that activation of the GHB receptor in some brain areas results in the release of [[glutamate]], the principal excitatory neurotransmitter.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref> Drugs that selectively activate the GHB receptor cause absence seizures in high doses, as do GHB and [[GABA]]<sub>B</sub> agonists.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref>
 Activation of both the GHB receptor and [[GABA]]<sub>B</sub> is responsible for the addictive profile of GHB. GHB's effect on dopamine release is biphasic.<ref>Drosophila [[GABA]]<sub>B</sub> receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB) | http://www.sciencedirect.com/science/article/pii/S0014299905007442</ref> Low concentrations stimulate dopamine release via the GHB receptor.<ref>A specific gamma-hydroxybutyrate receptor ligand possesses both antagonistic and anticonvulsant properties | http://www.ncbi.nlm.nih.gov/pubmed/2173754</ref> Higher concentrations inhibit dopamine release via [[GABA]]<sub>B</sub> receptors as do other [[GABA]]<sub>B</sub> [[agonists]] such as [[baclofen]] and [[phenibut]].<ref>Tonic GABA-ergic modulation of striatal dopamine release studied by in vivo microdialysis in the freely moving rat | http://www.sciencedirect.com/science/article/pii/001429999500369V</ref> After an initial phase of inhibition, [[dopamine]] release is then increased via the GHB receptor.