Does gamma-hydroxybutyrate inhibit or stimulate central DA release?

Gamma-hydroxybutyrate (GHB), a four-carbon fatty acid and anaesthetic, is widely considered to be a relatively specific inhibitor of central dopamine (DA) release. The inhibitory effect of GHB on the latter is thought to occur as a consequence of its diminution of impulse flow in central dopaminergic neurons. However, a number of studies have recently reported that GHB primarily stimulates rather than inhibits central DA release, with any inhibitory effect produced of a modest and transitory nature. GHB has been and continues to be widely used as an important research tool largely because it is one of only a few drugs available that acts primarily on DA release. Consequently, it is important to determine whether GHB inhibits DA release as previously thought, or stimulates DA release, as more recently suggested. Following a critical review of the literature, the present report suggests that GHB does inhibit rather than stimulate presynaptic DA release in consonance with its behavioral and pharmacological activity. Recent in vivo studies indicating that GHB stimulates DA release were done under anaesthesia or in the presence of a high concentration of calcium. Both conditions have been found to spuriously enhance striatal DA release in vivo, which may account for the failure of some studies to observe an inhibitory effect of GHB on DA release in vivo.