Gamma-hydroxybutyrate (GHB) reduces operant behavior without impairing working memory in rats responding under fixed-consecutive-number schedules

Laraway, Sean; Snycerski, Susan; Baker, Lisa E.; Poling, Alan

doi:10.1016/j.pbb.2007.08.002

Cited by 11 publications

(5 citation statements)

References 55 publications

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“…Three studies have reported that repeated administration of GHB to rats impaired spatial learning and memory (Sircar and Basak 2004; García et al 2006; Kueh et al 2008). Other studies have shown that acute doses of GHB did not impair working memory or cognitive (Go/No-go) task performance in rats and rhesus monkeys, respectively (Nakamura et al 1987; Laraway et al 2007). …”

Section: Introductionmentioning

confidence: 94%

Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers

2009

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Rationale Illicit gamma-hydroxybutyrate (GHB) has received attention as a “date rape drug” that produces robust amnesia; however, there is little experimental evidence in support of GHB’s amnestic effects. Objectives This study compared the cognitive effects of GHB (sodium oxybate) with those of triazolam in healthy volunteers. Materials and methods Doses of sodium oxybate (1.125, 2.25, and 4.5 g/70 kg), triazolam (0.125, 0.25, and 0.5 mg/70 kg), and placebo were administered to 15 volunteers under repeated measures, counterbalanced, double-blind, double-dummy conditions. The time course and peak physiological, psychomotor, subjective, and cognitive effects were examined. Results Sodium oxybate and triazolam produced similar increases in participant ratings of drug effects. Performance on psychomotor, working memory, and episodic memory tasks was impaired to a greater extent after triazolam than sodium oxybate. Conclusions Together, these data suggest that sodium oxybate produces less psychomotor and cognitive impairment than triazolam at doses that produce equivalent participant-rated subjective effects in healthy volunteers.

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Section: Introductionmentioning

confidence: 94%

Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers

2009

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“…Two studies reported that repeated doses of 100 mg/kg GHB (ip) impaired spatial learning and memory in rats (Sircar and Basak, 2004; García et al, 2006); other studies reported that single doses of GHB did not impair working memory or cognitive (Go/No-go) task performance in rats (up to 500 mg/kg, ip) and rhesus monkeys (up to 250 mg/kg, ig), respectively (Nakamura et al, 1987; Laraway et al, 2008). Data from experimental studies in humans suggest that doses of 10 mg/kg, iv and 4 g/70 kg, po of GHB can affect working memory and the encoding of episodic memory (Grove-White and Kelman, 1971; Carter et al, 2006b); however, the precise mechanism of action underlying these effects of GHB on memory and cognition is not established.…”

Section: Behavioral Effects Of Ghbmentioning

confidence: 99%

Behavioral analyses of GHB: Receptor mechanisms

Carter

Koek

France

2009

Pharmacology & Therapeutics

137

110

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GHB is used therapeutically and recreationally, although the precise mechanism of action responsible for its different behavioral effects is not entirely clear. The purpose of this review is to summarize how behavioral procedures, especially drug discrimination procedures, have been used to study the mechanism of action of GHB. More specifically, we will review several different drug discrimination procedures and discuss how they have been used to qualitatively and quantitatively study different components of the complex mechanism of action of GHB. A growing number of studies have provided evidence that the behavioral effects of GHB are mediated predominantly by GABA B receptors. However, there is also evidence that the mechanisms mediating the effects of GHB and the prototypical GABA B receptor agonist baclofen are not identical, and that other mechanisms such as GHB receptors and subtypes of GABA A and GABA B receptors might contribute to the effects of GHB. These findings are consistent with the different behavioral profile, abuse liability, and therapeutic indications of GHB and baclofen. A better understanding of the similarities and differences between GHB and baclofen, as well as the pharmacological mechanisms of action underlying the recreational and therapeutic effects of GHB, could lead to more effective medications with fewer adverse effects.

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“…Navarro and coworkers studied the effects of chronic low doses of GHB (5–100 mg/kg for 12 – 30 days) on the “hole-board” task performance in adult mice, and reported that working memory was significantly reduced in GHB-treated mice compared to controls (Davila et al , 2004; Garcia et al , 2006; Luna et al , 2002). In another study, GHB was reported to decrease operant behavior but not working memory in adult rats (Laraway et al , 2008). Earlier, our laboratory has shown that repeated GHB exposure in adolescent male (Sircar and Basak, 2004) and female (Sircar et al , 2008) rats significantly impaired the acquisition of spatial learning and memory.…”

Section: Introductionmentioning

confidence: 97%

Effects of γ-hydroxybutyric acid on spatial learning and memory in adolescent and adult female rats

Sircar

Basak

Sircar

et al. 2010

Pharmacology Biochemistry and Behavior

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Abstractγ-hydroxybutyric acid (GHB) has been reported to disrupt spatial learning and memory in adolescent male rats. The present study was undertaken to determine the effects of GHB on the acquisition of spatial memory in adolescent female rats, and to investigate age specificity of the behavioral impairments. Adolescent female rats were subjected to repeated GHB or saline administrations, and tested in the Morris water maze. Compared to age-matched saline controls, adolescent GHB-treated rats took significantly longer and swam greater distances to find the hidden platform. In the probe trial, GHB-treated adolescent rats spent less time in the target quadrant than saline-treated controls. There was no difference in either the swim speed or in the visual task performance between GHB-treated and saline-treated rats. To test for ontogenic specificity of the behavioral responses, adult female rats were treated with GHB and tested behaviorally in two separate experiments using a 6-day learning protocol (Experiment 1) and a 16-day learning protocol (Experiment 2). In the 6-day spatial learning and memory task, adult salinetreated rats failed to learn the task, and GHB did not alter the latency to find the platform, or performance in the probe trial. In the second behavioral protocol, a modified version of the memory task was used to test adult animals. The number of test days was increased from 6 days to 16 days. Adult saline-treated females learned the task in the 16-days protocol. But unlike in adolescent female rat, GHB in adult rats had minimal effects on reference memory even when they had learned the spatial memory task. Performances in the probe trial by GHB-treated rats and saline controls were similar. Together, these data suggest that GHB impairs spatial learning specifically in adolescent female rats.

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Gamma-hydroxybutyrate (GHB) reduces operant behavior without impairing working memory in rats responding under fixed-consecutive-number schedules

Cited by 11 publications

References 55 publications

Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers

Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers

Behavioral analyses of GHB: Receptor mechanisms

Effects of γ-hydroxybutyric acid on spatial learning and memory in adolescent and adult female rats

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