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

Area of Science:

• Neuroimaging
• Pharmacology
• Neuroscience

Background:

• γ-hydroxybutyrate (sodium oxybate [SO]) is a sedative and anti-narcoleptic medication with abuse potential.
• Previous studies in non-human primates suggested SO may inhibit striatal dopamine release.

Purpose of the Study:

• To investigate whether SO transiently inhibits striatal dopamine release in humans using neuroimaging.
• To explore the relationship between SO dosage, dopamine release, and subjective effects like drowsiness.

Main Methods:

• Positron emission tomography (PET) with [C-11]raclopride, a D2/3 dopamine receptor radioligand, was used in 10 healthy participants and 1 narcolepsy patient.
• Participants received a 3g oral dose of SO, with PET scans conducted at 1 and 7 hours post-administration.
• Plasma SO levels and duration of drowsiness were monitored.

Main Results:

• No significant overall changes in striatal [C-11]raclopride binding (dopamine occupancy) were observed 1 or 7 hours after SO administration.
• A small, non-significant increase in binding (implying decreased dopamine occupancy) was noted in the limbic striatal subdivision at 1 hour post-SO (+6.5% in healthy, +13.2% in narcolepsy patient).
• A positive correlation was found between the duration of drowsiness and the change in [C-11]raclopride binding in the limbic striatum (r=0.73, p=0.017).

Conclusions:

• This exploratory study did not find robust evidence of striatal dopamine changes in humans following a 3g dose of SO, contrary to findings in non-human primates.
• Preliminary data suggest a possible slight, transient inhibition of dopamine release in the limbic striatum, which may be related to subjective drowsiness.