Effect of gamma-hydroxybutyrate on central dopamine release in vivo. A microdialysis study in awake and anesthetized animals.

gamma-Hydroxybutyrate (GHB) is generally considered to be an inhibitor of striatal dopamine (DA) release. However, a number of recent reports and at least one major review suggest that GHB enhances rather than inhibits striatal DA release. To examine this discrepancy, the effect of GHB on striatal DA release was monitored for 2 hr by microdialysis in awake and urethane-anesthetized rats. GHB (500 mg/kg, i.p.) significantly inhibited striatal DA release in conscious animals. However, anesthetic pretreatment completely abolished the inhibitory effect of GHB on DA release. In urethane-anesthetized animals, intraperitoneal injections of GHB resulted in a dialysis DA output that was the same as basal and saline control levels for all but the last three intervals where DA release was elevated slightly. In contrast to the intraperitoneal route, subcutaneous injections of GHB in anesthetized animals produced significant elevations of DA release above baseline levels. The increases ranged from 125 to 133% of basal levels. These results indicate that while GHB enhances striatal DA release in anesthetized animals, it inhibits rather than enhances this release in awake animals. This would explain why GHB induces an inhibition of DA-release-dependent behaviors rather than an enhancement. The results also indicate that the route of GHB administration influences its effects on striatal DA release, at least in anesthetized animals.