Adolescent ?-hydroxybutyric acid exposure decreases cortical -methyl--aspartate receptor and impairs spatial learning

Sircar, Ratna; Basak, Ashim Kumar

doi:10.1016/j.pbb.2004.09.022

Cited by 32 publications

(22 citation statements)

References 48 publications

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“…Thus, GHB-induced disruption was specific to the acquisition of contextual memory without affecting acquisition of cued conditioning or expression of contextual or cued memory. The present findings are in line with our previous findings using the water maze where it was shown that repeated administration of GHB (100 mg/kg) in adolescent female rats disrupted the acquisition of spatial memory, but not its expression [51,52,53].…”

Section: Discussionsupporting

confidence: 93%

“…When tested in the hidden platform task using the Morris water maze for reference memory, compared to control rats GHB-treated rats took significantly longer and swam greater lengths to find the hidden platform, and their performance during the probe trial was significantly compromised. There was little effect on motoric or motivational functions since performance in the visual cued task did not differ between drug-treated and control rats [51,52,53].…”

Section: Introductionmentioning

confidence: 91%

“…Female adolescent rats were used for the study since our earlier studies showed GHB-induced spatial memory deficits in female adolescent rats [51,52,53]. Rats were group-housed in plastic cages with ad libitum access to food and water in a temperature-and humidity-controlled animal care facility with a 12 h light/12 h dark cycle.…”

Section: Subjectsmentioning

confidence: 99%

“…Drug and saline solutions were injected intraperitoneally (IP) in a volume of 1 mL/kg. Doses of GHB used were based upon our previous studies [51,52,53].…”

Section: Drug and Drug Solutionmentioning

confidence: 99%

“…GHB's amnesia-causing effect is associated with its short half-life and rapid clearance rate [2,8,16,61,66]. In experimental animals, GHB has been shown to cause memory deficits [27,42,51,52,53,62]. We have earlier reported that GHB given to adolescent rats cause significant deficits in spatial learning and memory.…”

Section: Introductionmentioning

confidence: 99%

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Systemic Administration of γ-Hydroxybutyric Acid in Adolescent Rat Impairs Contextual Fear Conditioning, But Not Cued Conditioning

Sircar

Ishiwari²

2014

Journal of Drug and Alcohol Research

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γ-hydroxybutyric acid (GHB) causes retrograde amnesia in juveniles and young adults. Earlier, we have reported that in adolescent rat, GHB impairs the hidden platform task performance in the Morris water maze. In the present study, a classical fear conditioning paradigm was used to examine the effects of GHB on the acquisition of contextual conditioning, a hippocampus-dependent associative task, and cued tone conditioning, a hippocampus-independent task, in adolescent rats. Administration of GHB before the presentation of tone-shock pairings dose-dependently disrupted the acquisition of contextual conditioning with no effect on tone conditioning, when conditioned fear was measured 24 h later. Administering GHB prior to testing did not disrupt either contextual or tone conditioning. These results demonstrate that in the adolescent rat exposure to GHB preferentially disrupt hippocampal-dependent learning.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 91%

Section: Subjectsmentioning

confidence: 99%

“…Drug and saline solutions were injected intraperitoneally (IP) in a volume of 1 mL/kg. Doses of GHB used were based upon our previous studies [51,52,53].…”

Section: Drug and Drug Solutionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Systemic Administration of γ-Hydroxybutyric Acid in Adolescent Rat Impairs Contextual Fear Conditioning, But Not Cued Conditioning

Sircar

Ishiwari²

2014

Journal of Drug and Alcohol Research

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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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Individual differences in GHB consumption in a new voluntary GHB self-administration model in outbred rats

Wolf,

Spoelder,

Beurmanjer

et al. 2024

Psychopharmacology

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Background and purpose The use of the recreational drug gamma-hydroxybutyric acid (GHB) has increased over the past decade, concomitantly leading to a higher incidence of GHB use disorder. Evidence-based treatment interventions are hardly available and cognitive effects of long-term GHB use remain elusive. In order to study the development of GUD and the causal effects of chronic GHB consumption, a GHB self-administration model is required. Experimental approach Long Evans rats had access to GHB in their home cage according to a two-bottle choice procedure for 3 months. Intoxication and withdrawal symptoms were assessed using an automated sensor-based setup for longitudinal behavioral monitoring. Rats were trained in an operant environment according to a fixed ratio (FR) 1, 2, and 4 schedule of reinforcement. Addiction-like behaviors were assessed through progressive ratio-, non-reinforced-, and quinine-adulterated operant tests. In addition, the novel object recognition test and elevated plus maze test were performed before and after GHB self-administration to assess memory performance and anxiety-like behavior, respectively. Key results All rats consumed pharmacologically relevant levels of GHB in their home cage, and their intake remained stable over a period of 3 months. No clear withdrawal symptoms were observed following abstinence. Responding under operant conditions was characterized by strong inter-individual differences, where only a subset of rats showed high motivation for GHB, habitual GHB-seeking, and/or continued responding for GHB despite an aversive taste. Male rats showed a reduction in long-term memory performance 3 months after home-cage GHB self-administration. Anxiety-like behavior was not affected by GHB self-administration. Conclusion and implications The GHB self-administration model was able to reflect individual susceptibility for addiction-like behavior. The reduction in long-term memory performance upon GHB self-administration calls for further research into the cognitive effects of chronic GHB use in humans.

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Adolescent ?-hydroxybutyric acid exposure decreases cortical -methyl--aspartate receptor and impairs spatial learning

Cited by 32 publications

References 48 publications

Systemic Administration of γ-Hydroxybutyric Acid in Adolescent Rat Impairs Contextual Fear Conditioning, But Not Cued Conditioning

Systemic Administration of γ-Hydroxybutyric Acid in Adolescent Rat Impairs Contextual Fear Conditioning, But Not Cued Conditioning

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

Individual differences in GHB consumption in a new voluntary GHB self-administration model in outbred rats

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