Oliver G Bosch1,2, Fabrizio Esposito3, Dario Dornbierer1,2, Robin von Rotz1,2, Rainer Kraehenmann1, Philipp Staempfli1,4, Boris B Quednow2,5, Erich Seifritz1,5. 1. Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital of the University of Zurich, Zurich, Switzerland. 2. Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital of the University of Zurich, Zurich, Switzerland. 3. Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Italy. 4. MR-Center of the Department of Psychiatry, Psychotherapy and Psychosomatics and the Department of Child and Adolescent Psychiatry, Psychiatric Hospital of the University of Zurich, Zurich, Switzerland. 5. Neuroscience Center Zurich, University and ETH, Zurich, Switzerland.
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 aplacebo-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.
RCT Entities:
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.
Authors: Ishtiaq Mawla; Eric Ichesco; Helge J Zöllner; Richard A E Edden; Thomas Chenevert; Henry Buchtel; Meagan D Bretz; Heather Sloan; Chelsea M Kaplan; Steven E Harte; George A Mashour; Daniel J Clauw; Vitaly Napadow; Richard E Harris Journal: Arthritis Rheumatol Date: 2021-05-31 Impact factor: 15.483