Effects of γ-hydroxybutyrate (GHB) and its metabolic precursors on delayed-matching-to-position performance in rats Daniel Kueh, Kazuhiro Iwamoto, Alan Poling ⁎ , Lisa E. Baker Department of Psychology, Western Michigan University, Kalamazoo, MI 49008, USA Received 27 August 2007; received in revised form 21 November 2007; accepted 5 December 2007 Available online 14 December 2007 Abstract The purpose of the present study was to provide further information about the effects of γ-hydroxybutyrate (GHB) on memory. Initially, the acute effects of gamma-butyrolactone (GBL, 75-200 mg/kg IP), 1,4-butanediol (1,4-BD, 100–300 mg/kg IP), and ethanol (1.0–3.0 g/kg, oral), as well as GHB (100–300 mg/kg IP), were examined in rats responding under a delayed-matching-to-position (DMTP) procedure with delays from 0 to 32 s. Acute administration of all four drugs reduced the number of trials completed and also reduced accuracy during delay trials, but not during trials without a delay. Some tolerance developed to the disruptive effects of GHB following exposure to 300 mg/kg/day for 29 consecutive days. These data indicate that GHB can disrupt working memory and speed of responding, and that tolerance can develop to these effects. Moreover, the acute effects of GHB under the DMTP procedure resemble those of its metabolic precursors, GBL and 1,4-BD, and of the prototypical CNS depressant drug, ethanol. © 2008 Elsevier Inc. All rights reserved. Keywords: GHB; GBL; 1,4-BD; Ethanol; Delayed-matching-to-position; Memory; Tolerance; Rats 1. Introduction γ-Hydroxybutyrate (GHB) is both a precursor of GABA and a neurotransmitter in the mammalian central nervous system. As a neurotransmitter, GHB is thought to bind to either a GABA B receptor (Carter et al., 2003) or a specific GHB metabotropic receptor (Snead, 2000). Artificially synthesized by Laborit in 1960 (Tunnicliff, 1997), GHB is now used in some countries for the treatment of cataplexy and is being evaluated as a treatment for alcohol and opiate addiction (Fuller and Hornfeldt, 2003; Fuller et al., 2004; Gallimberti et al., 1989; Gallimberti et al., 1993). Nevertheless, GHB poses potential health risks (Gallo- way et al., 1997). GHB has been recognized as a “date rape” drug by the news media and historically has been popular among drug users at “rave parties” (Schwartz et al., 2000), although recent findings suggest that the drug is most often used at private residences these days (Barker et al., 2007). The two precursors of GHB, GBL and 1,4-BD, are found in some commercial solvents and might pose risks similar to those of GHB (Nicholson and Balster, 2001; Tarabar and Nelson, 2004). For example, their is a case report of 1,4-BD-induced intoxi- cation in a person who intentionally ingested “liquid ecstasy” (Lora-Tamayo et al., 2003). Memory impairment is one of the potential adverse effects of GHB. In an early study with humans, Grove-White and Kelman (1971) found significant short-term memory deficits in a digit recognition task after intravenous administration of GHB to healthy individuals when the retention interval was 20 s, but not when it was 4 s. Carter et al. (2006), who examined the effects of a broad range of orally-administered GHB doses (2–18 g/ 70 kg) in a complex test battery, also reported GHB-induced memory impairment, although it was weaker than that produced by triazolam (0.5 and 1 mg/70 kg) or pentobarbital (200 and 400 mg/70 kg). Nonhuman research affords an opportunity to explore the effects of GHB on memory under tightly controlled conditions, and some relevant investigations have appeared. For example, Available online at www.sciencedirect.com Pharmacology, Biochemistry and Behavior 89 (2008) 179 – 187 www.elsevier.com/locate/pharmbiochembeh ⁎ Corresponding author. Present address: Department of Psychology, Western Michigan University, Kalamazoo MI 49008-5439, USA. Tel.: +1 269 387 4483; fax: +1 269 387 4550. E-mail address: alan.poling@wmich.edu (A. Poling). 0091-3057/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.pbb.2007.12.007