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Prohedonic properties of gamma-hydroxybutyrate are associated with changes in limbic resting-state functional connectivity


Bosch, Oliver G; Esposito, Fabrizio; Dornbierer, Dario; von Rotz, Robin; Kraehenmann, Rainer; Staempfli, Philipp; Quednow, Boris B; Seifritz, Erich (2018). Prohedonic properties of gamma-hydroxybutyrate are associated with changes in limbic resting-state functional connectivity. Human Psychopharmacology: Clinical and Experimental, 33(6):e2679.

Abstract

Objective Gamma‐hydroxybutyrate (GHB) is an endogenous GHB‐/GABA‐B receptor agonist and a narcolepsy treatment. However, GHB is also abused for its prohedonic effects. On a neuronal level, it was shown that GHB increases regional cerebral blood flow in limbic areas such as the right anterior insula (rAI) and the anterior cingulate cortex (ACC). We aimed to further explore the association between the subjective and neuronal signatures of GHB.
Method We assessed subjective effects and resting‐state functional connectivity (rsFC) of an rAI‐ and an ACC‐seed in 19 healthy male subjects after GHB (35 mg/kg p.o.) using a placebo‐controlled, double‐blind, randomized, cross‐over functional magnet resonance imaging design.
Results GHB increased subjective ratings for euphoria (p < 0.001) and sexual arousal (p < 0.01). Moreover, GHB increased rAI‐rsFC to the right thalamus and the superior frontal gyrus and decreased ACC‐rsFC to the bilateral paracentral lobule (all p < 0.05, cluster corrected). Moreover, GHB‐induced euphoria was associated with rAI‐rsFC to the superior frontal gyrus (p < 0.05, uncorrected).
Conclusions GHB induces prohedonic effects such as euphoria and sexual arousal and in parallel modulates limbic rsFC with areas linked to regulation of mood, cognitive control, and sexual experience. These results further elucidate the drug's effects in neuropsychiatric disorders and as drug of abuse.

Abstract

Objective Gamma‐hydroxybutyrate (GHB) is an endogenous GHB‐/GABA‐B receptor agonist and a narcolepsy treatment. However, GHB is also abused for its prohedonic effects. On a neuronal level, it was shown that GHB increases regional cerebral blood flow in limbic areas such as the right anterior insula (rAI) and the anterior cingulate cortex (ACC). We aimed to further explore the association between the subjective and neuronal signatures of GHB.
Method We assessed subjective effects and resting‐state functional connectivity (rsFC) of an rAI‐ and an ACC‐seed in 19 healthy male subjects after GHB (35 mg/kg p.o.) using a placebo‐controlled, double‐blind, randomized, cross‐over functional magnet resonance imaging design.
Results GHB increased subjective ratings for euphoria (p < 0.001) and sexual arousal (p < 0.01). Moreover, GHB increased rAI‐rsFC to the right thalamus and the superior frontal gyrus and decreased ACC‐rsFC to the bilateral paracentral lobule (all p < 0.05, cluster corrected). Moreover, GHB‐induced euphoria was associated with rAI‐rsFC to the superior frontal gyrus (p < 0.05, uncorrected).
Conclusions GHB induces prohedonic effects such as euphoria and sexual arousal and in parallel modulates limbic rsFC with areas linked to regulation of mood, cognitive control, and sexual experience. These results further elucidate the drug's effects in neuropsychiatric disorders and as drug of abuse.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
04 Faculty of Medicine > Neuroscience Center Zurich
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Pharmacology (medical), Neurology, Psychiatry and Mental health, Clinical Neurology
Language:English
Date:1 November 2018
Deposited On:29 Nov 2018 11:20
Last Modified:30 Nov 2018 08:36
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0885-6222
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/hup.2679
PubMed ID:30426556

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Language: English
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Embargo till: 2019-11-13