From the street to the brain: neurobiology of the recreational drug gamma-hydroxybutyric acid.
gamma-Hydroxybutyric acid (GHB) is a short-chain fatty acid that occurs naturally in the mammalian brain and is formed primarily from the precursor gamma-aminobutyric acid (GABA). The properties of GHB suggest that it has a neuromodulatory role in the brain and has the ability to induce several pharmacological and behavioral effects. GHB has been used clinically as an anesthetic and to treat alcoholism and narcolepsy. Furthermore, GHB has emerged recently as a major recreational drug of abuse. GHB appears to have dual mechanisms of action in the brain. Biochemical data suggest that the intrinsic neurobiological activity of GHB might be mediated through the GHB receptor, which is separate and distinct from the GABA(B) receptor. However, many of the pharmacological and clinical effects of exogenously administered GHB, including the properties of addiction, tolerance, withdrawal and intoxication, are probably mediated via the GABA(B) receptor, where GHB might act both directly as a partial agonist and indirectly through GHB-derived GABA.
Wong
C Guin Ting
CG
Institute of Medical Sciences, and Brain and Behavior Research Program, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Gibson
K Michael
KM
Snead
O Carter
OC
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006885:Hydroxybutyrates / Q000009:adverse effects / Q000494:pharmacology*; D013287:Illicit Drugs / Q000494:pharmacology; D009446:Neurobiology / Q000639:trends*; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
C039403:4-hydroxybutyric acid receptor; D006885:Hydroxybutyrates; D013287:Illicit Drugs; D011956:Receptors, Cell Surface; D018080:Receptors, GABA-B; C111420:4-hydroxybutyric acid