Gamma-Hydroxybutyrate, a Normal Brain Metabolite

Bessman, Samuel P.; Fishbein, William N.

doi:10.1038/2001207a0

Cited by 215 publications

(80 citation statements)

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“…,),-Hydroxybutyrate (GHB) was chosen as a metabolic depressant. It is a naturally occurring substance in mammalian brain (Bessman and Fishbein, 1963;Roth, 1970;Roth and Giarman, 1970). Its pharmacological effects have been re viewed recently (Snead, 1977).…”

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confidence: 99%

Influence of γ-Hydroxybutyrate on the Relationship between Local Cerebral Glucose Utilization and Local Cerebral Blood Flow in the Rat Brain

Kuschinsky

Suda

Sokoloff

1985

J Cereb Blood Flow Metab

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Summary:The relationship between local cerebral glu cose utilization (LCGU) and local CBF (LCBF) was ex amined during the action of ,(-hydroxybutyrate (GHB) (900 mg/kg i. v.) in conscious rats. GHB induced dis crepant effects on blood flow and metabolism. LCGU was markedly depressed in all structures examined, whereas LCBF was differently affected in that no related changes were observed. Global glucose utilization was markedly depressed ( -51%), whereas global blood flowThe close correlation between metabolism and blood flow in the brain has recently been assessed by direct measurement of local cerebral glucose uti lization (LCGU) and local CBF (LCBF) in a variety of cerebral structures (Sokoloff, 1978;Kuschinsky et al., 1981; McCulloch et al., 1982a;Nakai et al., 1983). The mechanism that mediates this relation ship is not yet understood. Numerous studies have been carried out to elucidate the mechanism of the hyperemia that accompanies functional activation of the brain. Under these conditions, hyperemia ap pears to be triggered by the increased release of metabolically linked vasodilator substances. A number of candidates exist for such a local meta bolic control, e.g., H+, K +, adenosine, etc. [for references see Kuschinsky and Wahl (1978) and Kuschinsky (1982)], because their extravascular concentrations increase during functional activation to levels that induce vasodilation of pial arteries. Whereas such local metabolic factors seem to be mediators of hyperemia induced by acute functional Received June 19,1984; accepted October 17, 1984. Address correspondence and reprint requests to Prof. Dr. W. Kuschinsky at Department of Physiology, University of Bonn, Nussallee 11, 0-5300 Bonn 1, F.R. G, Abbreviations used: GHB, -y-hydroxybutyrate; LCBF, local CB F; LCGU , local cerebral glucose utilization. 58was not significantly altered. The marked dissociation be tween the changes in global glucose utilization and global blood flow induced by GHB is reflected only to a minor degree in the local values inasmuch as the correlation between LCGU and LCBF was only slightly weakened and its heterogeneity was increased. Key Words: 2-Deox yglucose-Iodoantipyrine-Local blood flow -Local coupling-Local metabolism-Rat brain.activation, the question still remains as to whether these factors are also responsible for the heteroge neity of LCBF that under normal conditions is closely correlated with local metabolism (Sokoloff, 1978;Kuschinsky et al., 1981; McCulloch et al., 1982a;Nakai et al., 1983).To investigate this question, the influence of marked metabolic depression on the relationship between local cerebral metabolism and blood flow was examined. ,),-Hydroxybutyrate (GHB) was chosen as a metabolic depressant. It is a naturally occurring substance in mammalian brain (Bessman and Fishbein, 1963;Roth, 1970;Roth and Giarman, 1970). Its pharmacological effects have been re viewed recently (Snead, 1977). As shown earlier for ,),-butyrolactone (Wolfson et al., 1977), GHB in high doses apparently reduces global cerebral energy...

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confidence: 99%

Influence of γ-Hydroxybutyrate on the Relationship between Local Cerebral Glucose Utilization and Local Cerebral Blood Flow in the Rat Brain

Kuschinsky

Suda

Sokoloff

1985

J Cereb Blood Flow Metab

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“…GHB, a metabolite and a structural analog of GABA, is found endogenously throughout the mammalian brain in micromolar concentrations [5,11,32]. GHB has been used therapeutically in the treatment of sleep disorders [19,29,60,64], and to treat alcoholism and alcohol-withdrawal symptoms [7].…”

Section: Introductionmentioning

confidence: 99%

Systemic Administration of γ-Hydroxybutyric Acid in Adolescent Rat Impairs Contextual Fear Conditioning, But Not Cued Conditioning

Sircar

Ishiwari²

2014

Journal of Drug and Alcohol Research

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γ-hydroxybutyric acid (GHB) causes retrograde amnesia in juveniles and young adults. Earlier, we have reported that in adolescent rat, GHB impairs the hidden platform task performance in the Morris water maze. In the present study, a classical fear conditioning paradigm was used to examine the effects of GHB on the acquisition of contextual conditioning, a hippocampus-dependent associative task, and cued tone conditioning, a hippocampus-independent task, in adolescent rats. Administration of GHB before the presentation of tone-shock pairings dose-dependently disrupted the acquisition of contextual conditioning with no effect on tone conditioning, when conditioned fear was measured 24 h later. Administering GHB prior to testing did not disrupt either contextual or tone conditioning. These results demonstrate that in the adolescent rat exposure to GHB preferentially disrupt hippocampal-dependent learning.

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“…Gamma-hydroxybutyrate (GHB) is an endogenous short-chain fatty acid neuromodulator which is biosynthetically derived from the major inhibitory neurotransmitter gamma-aminobutyrate (GABA) (Bessman and Fishbein, 1963). It appears to bind to specific GHB-and GABA B -receptors (Snead, 2000).…”

Section: Introductionmentioning

confidence: 99%

Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting plasma oxytocin and testosterone

Bosch

Eisenegger

Gertsch

et al. 2015

Psychoneuroendocrinology

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Word count main text:4734 Word count abstract: 200 Number of references: 59Number of tables: 2 ABSTRACTGamma-hydroxybutyrate (GHB) is a GHB-/GABA B -receptor agonist. Reports from GHB abusers indicate euphoric, prosocial, and empathogenic effects of the drug. We measured the effects of GHB on mood, prosocial behavior, social and non-social cognition and assessed potential underlying neuroendocrine mechanisms. GHB (20 mg/kg) was tested in 16 healthy males, using a randomized, placebo-controlled, cross-over design. Subjective effects on mood were assessed by visual-analoguescales and the GHB-Specific-Questionnaire. Prosocial behavior was examined by the Charity Donation Task, the Social Value Orientation test, and the Reciprocity Task. Reaction time, memory, empathy, and theory-of-mind were also tested. Blood plasma levels of GHB, oxytocin, testosterone, progesterone, dehydroepiandrosterone (DHEA), cortisol, aldosterone, and adrenocorticotropichormone (ACTH) were determined. GHB showed stimulating and sedating effects, and elicited euphoria, disinhibition, and enhanced vitality. In participants with low prosociality, the drug increased donations and prosocial money distributions. In contrast, social cognitive abilities such as emotion recognition, empathy, and theory-of-mind, and basal cognitive functions were not affected.GHB increased plasma progesterone, while oxytocin and testosterone, cortisol, aldosterone, DHEA, and ACTH levels remained unaffected. GHB has mood-enhancing and prosocial effects without affecting social hormones such as oxytocin and testosterone. These data suggest a potential involvement of GHB-/GABA B -receptors and progesterone in mood and prosocial behavior.

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Gamma-Hydroxybutyrate, a Normal Brain Metabolite

Cited by 215 publications

References 4 publications

Influence of γ-Hydroxybutyrate on the Relationship between Local Cerebral Glucose Utilization and Local Cerebral Blood Flow in the Rat Brain

Influence of γ-Hydroxybutyrate on the Relationship between Local Cerebral Glucose Utilization and Local Cerebral Blood Flow in the Rat Brain

Systemic Administration of γ-Hydroxybutyric Acid in Adolescent Rat Impairs Contextual Fear Conditioning, But Not Cued Conditioning

Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting plasma oxytocin and testosterone

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