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

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.

Greater Somatosensory Afference With Acupuncture Increases Primary Somatosensory Connectivity and Alleviates Fibromyalgia Pain via Insular γ‐Aminobutyric Acid: A Randomized Neuroimaging Trial

“…Few studies have noted treatment‐related changes in GABA and functional connectivity. It was found in one study that administration of Gamma‐hydroxybutyrate (a GABA agonist) increased right anterior insula functional connectivity (48). Due to the complex relationship between GABA and BOLD functional connectivity demonstrated across previous studies, our results need further validation.…”

Does sodium oxybate inhibit brain dopamine release in humans? An exploratory neuroimaging study

“…We also found, in one participant who showed decreased [C-11] raclopride binding in LST (i.e., increased dopamine), transient euphoria, a known (Bosch et al, 2018) but, in clinical trials, an uncommon event (Xyrem Product Monograph, 2018), potentially implicating limbic brain activation reported after SO (see Bosch et al, 2018). This raises the possibility that some might respond to SO with initial increase in dopamine release and consequent stimulant-like behavioral activation.…”

“…Sodium oxybate (SO; the sodium salt of γ-hydroxybutyrate) is a sedative drug used for treatment of cataplexy and excessive daytime sleepiness in narcolepsy (Carter et al, 2006;Xyrem Product Monograph, 2018). It may also be abused by recreational users (see Bosch et al, 2018). The brain mechanisms explaining effects of this endogenous GABA metabolite are not known, but preclinical data show that a major action of the drug is likely to be activation of the brain GABA B receptor (Kaupmann et al, 2003).…”

A strange New Year’s Eve: triggers in Kleine-Levin syndrome

“…euphoria, disinhibition, enhanced vitality, amnesia, and has prosexual effects, for which the drug is used for illicit purposes (rape and theft). 7 Deep slow-wave sleep is induced at higher dosages, followed by coma and respiratory depression at very high dosages. The effects of GHB and alcohol are synergistic.…”