Synergistic interactions between 'club drugs': Gamma-hydroxybutyrate and phencyclidine enhance each other's discriminative stimulus effects

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Abstract

Gamma-hydroxybutyrate (GHB) is often abused together with other 'club drugs', such as the N-methyl-D-aspartate (NMDA) receptor antagonists ketamine and phencyclidine (PCP). We recently found that the NMDA antagonist dizocilpine markedly enhanced GHB-induced catalepsy in rats. The present studies explored the generality of this interaction. Different groups of rats were trained to discriminate 2 mg/kg PCP or 3.2 mg/kg of the γ-aminobutyric acid B receptor agonist baclofen from saline. In the PCP-trained rats, the dose-response (DR) curve for the discriminative stimulus (DS) effects of PCP was shifted 2.5-fold to the left by 178 mg/kg GHB, but not by baclofen. In the baclofen-trained rats, 2 mg/kg PCP shifted the DR curve for the baclofen-like DS effects of GHB 2.2-fold to the left, but did not shift the DR curve for baclofen. These results suggest that (i) NMDA antagonists potentiate not only the cataleptic effects of high doses of GHB, but also the DS effects of low doses, (ii) PCP and GHB enhance one another's DS effects, and (iii) this enhancement might be specific for GHB, because it did not occur with PCP and baclofen. These findings suggest that NMDA antagonists might potentiate the subjective effects of GHB in humans, and are further evidence that glutamatergic systems modulate effects of drugs of abuse.

Original languageEnglish (US)
Pages (from-to)807-810
Number of pages4
JournalBehavioural Pharmacology
Volume18
Issue number8
DOIs
StatePublished - Dec 2007

Fingerprint

Sodium Oxybate
Phencyclidine
Baclofen
Pharmaceutical Preparations
N-Methylaspartate
GABA-B Receptors
Aminobutyrates
Catalepsy
Dizocilpine Maleate
Ketamine
Street Drugs
N-Methyl-D-Aspartate Receptors

Keywords

  • Baclofen
  • Drug discrimination
  • Gamma-hydroxybutyrate
  • Phencyclidine
  • Rat

ASJC Scopus subject areas

  • Pharmacology
  • Neuroscience(all)

Cite this

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title = "Synergistic interactions between 'club drugs': Gamma-hydroxybutyrate and phencyclidine enhance each other's discriminative stimulus effects",
abstract = "Gamma-hydroxybutyrate (GHB) is often abused together with other 'club drugs', such as the N-methyl-D-aspartate (NMDA) receptor antagonists ketamine and phencyclidine (PCP). We recently found that the NMDA antagonist dizocilpine markedly enhanced GHB-induced catalepsy in rats. The present studies explored the generality of this interaction. Different groups of rats were trained to discriminate 2 mg/kg PCP or 3.2 mg/kg of the γ-aminobutyric acid B receptor agonist baclofen from saline. In the PCP-trained rats, the dose-response (DR) curve for the discriminative stimulus (DS) effects of PCP was shifted 2.5-fold to the left by 178 mg/kg GHB, but not by baclofen. In the baclofen-trained rats, 2 mg/kg PCP shifted the DR curve for the baclofen-like DS effects of GHB 2.2-fold to the left, but did not shift the DR curve for baclofen. These results suggest that (i) NMDA antagonists potentiate not only the cataleptic effects of high doses of GHB, but also the DS effects of low doses, (ii) PCP and GHB enhance one another's DS effects, and (iii) this enhancement might be specific for GHB, because it did not occur with PCP and baclofen. These findings suggest that NMDA antagonists might potentiate the subjective effects of GHB in humans, and are further evidence that glutamatergic systems modulate effects of drugs of abuse.",
keywords = "Baclofen, Drug discrimination, Gamma-hydroxybutyrate, Phencyclidine, Rat",
author = "Wouter Koek and Mandar Khanal and France, {Charles P}",
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T2 - Gamma-hydroxybutyrate and phencyclidine enhance each other's discriminative stimulus effects

AU - Koek, Wouter

AU - Khanal, Mandar

AU - France, Charles P

PY - 2007/12

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N2 - Gamma-hydroxybutyrate (GHB) is often abused together with other 'club drugs', such as the N-methyl-D-aspartate (NMDA) receptor antagonists ketamine and phencyclidine (PCP). We recently found that the NMDA antagonist dizocilpine markedly enhanced GHB-induced catalepsy in rats. The present studies explored the generality of this interaction. Different groups of rats were trained to discriminate 2 mg/kg PCP or 3.2 mg/kg of the γ-aminobutyric acid B receptor agonist baclofen from saline. In the PCP-trained rats, the dose-response (DR) curve for the discriminative stimulus (DS) effects of PCP was shifted 2.5-fold to the left by 178 mg/kg GHB, but not by baclofen. In the baclofen-trained rats, 2 mg/kg PCP shifted the DR curve for the baclofen-like DS effects of GHB 2.2-fold to the left, but did not shift the DR curve for baclofen. These results suggest that (i) NMDA antagonists potentiate not only the cataleptic effects of high doses of GHB, but also the DS effects of low doses, (ii) PCP and GHB enhance one another's DS effects, and (iii) this enhancement might be specific for GHB, because it did not occur with PCP and baclofen. These findings suggest that NMDA antagonists might potentiate the subjective effects of GHB in humans, and are further evidence that glutamatergic systems modulate effects of drugs of abuse.

AB - Gamma-hydroxybutyrate (GHB) is often abused together with other 'club drugs', such as the N-methyl-D-aspartate (NMDA) receptor antagonists ketamine and phencyclidine (PCP). We recently found that the NMDA antagonist dizocilpine markedly enhanced GHB-induced catalepsy in rats. The present studies explored the generality of this interaction. Different groups of rats were trained to discriminate 2 mg/kg PCP or 3.2 mg/kg of the γ-aminobutyric acid B receptor agonist baclofen from saline. In the PCP-trained rats, the dose-response (DR) curve for the discriminative stimulus (DS) effects of PCP was shifted 2.5-fold to the left by 178 mg/kg GHB, but not by baclofen. In the baclofen-trained rats, 2 mg/kg PCP shifted the DR curve for the baclofen-like DS effects of GHB 2.2-fold to the left, but did not shift the DR curve for baclofen. These results suggest that (i) NMDA antagonists potentiate not only the cataleptic effects of high doses of GHB, but also the DS effects of low doses, (ii) PCP and GHB enhance one another's DS effects, and (iii) this enhancement might be specific for GHB, because it did not occur with PCP and baclofen. These findings suggest that NMDA antagonists might potentiate the subjective effects of GHB in humans, and are further evidence that glutamatergic systems modulate effects of drugs of abuse.

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