Gamma-hydroxybutyrate (GHB) abuse is a growing medical and social concern. Media attention has recently focused on the rampant recreational use of this substance among America's youth, and its notorious involvement in numerous drug-facilitated sexual assaults. The precursors of GHB (GBL and 1,4-BD) are found in some industrial solvents and also present a potential health hazard because their supply is not easily controlled. Despite the fact that GHB has been used for medicinal purposes in Europe for nearly 30 years and was available over-the-counter in the U.S. until 1990, the neurobehavioral consequences of GHB abuse are not well understood. Research on the neurochemical mechanisms underlying GHB's behavioral and subjective effects is imperative to understanding the abuse potential of this drug and ultimately to developing treatments for GHB abuse. Preclinical studies that assess these mechanisms are an essential component of this research. One objective of this proposal is to characterize further the neuropharmacological mediation of GHB's discriminative stimulus effects. This will be accomplished using both two-choice and three-choice drug discrimination techniques in rats. Because other researchers have had some difficulty maintaining adequate stimulus control with GHB, methodological parameters will be experimentally assessed to determine the optimal conditions for establishing and maintaining GHB discrimination. Additionally, because very little is known about GHB's effects on learning and performance in preclinical models, a second objective is to investigate the effects of GHB in several behavioral assays that involve operant conditioning in rats. The acute and chronic effects of GHB will be examined in rats: (a) responding a multiple schedule during 10-hr sessions; (b) initially acquiring lever-press responding with immediate and delayed reinforcement; (c) performing a conditional discrimination under a fixed-consecutive number (FCN) schedule with and without an external discriminative stimulus; (d) performing a delayed conditional discrimination (DCD); and (e) performing under a multiple schedule of reinforcement with punishment in one component. Behavior under these assays is sensitive to other abused drugs. Therefore, these assays may be of value in characterizing the effects of GHB.
