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The first in vivo effects of GHB were described in 1964 as hypothermic, hypnotic, anesthetic, and anticonvulsant, and without marked respiratory depression or toxicity Since that time, the mechanisms underlying many of these effects have been further examined and elucidated. GHB and GBL (at 50200 mg/kg) produced EEG patterns similar to those observed during slow wave sleep and absence seizures in rats. The dopaminergic and opioidergic systems were initially implicated in the EEG effects of GHB because the absence seizure-like activity of GHB was blocked or reversed byd-amphetamine and naloxone, respectively
Serotonergic and dopaminergic agonists did not occasion responding on the GHB-appropriate lever. Thus, even early on, results from animals discriminating GHB suggested a role for GABA receptors, particularly GABABreceptors, in the behavioral effects of GHB.
There is substantial evidence that most, if not all, of the acute behavioral effects of GHB are mediated, at least in part, by GABAB receptors. In addition to discriminative stimulus effects, GABAB receptor antagonists have also been shown to attenuate GHBinduced changes in brain activity, neurotransmitter release
For the most part, drug discrimination studies have failed to support a role for GHB receptors in the discriminative stimulus effects of GHB. In animals discriminating GHB from vehicle, baclofen, or diazepam, the GHB stimulus does not appear to involve a prominent GHB receptormediated component. What remains, however, is a stimulus that appears to be mediated by a subtype of GABAB receptor.