Prohedonic Properties of Gamma-Hydroxybutyrate Are Associated with Changes in Limbic Resting-State Functional Connectivity.

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.