Behavioral effects of GHB

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

Discriminative stimulus effects of GHB

Consistent with studies in which the effects of GHB were examined in animals discriminating other drugs, GABAergic ligands tended to occasion the most GHB-appropriate responding.

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.

Effects of GHB in animals trained to discriminate GHB from other drugs

The effects of different selective GABAB receptor antagonists in animals trained to discriminate GHB from vehicle or other drug(s) suggested that subtypes of the GABAB receptor might be important in mediating the effects of GHB. If the discriminative stimulus effects of GHB and baclofen are identical, then animals should not be able to discriminate between the two drugs. However, if the effects of GHB and baclofen are not identical, then animals should be able to discriminate between GHB and baclofen.

Summary and future directions

A growing number of studies, particularly drug discrimination studies, have provided evidence that the behavioral effects of GHB are mediated predominantly by GABABreceptors.

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.