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Synergistic interactions between “club drugs”: GHB and PCP enhance each others discriminative stimulus effects
Author(s) -
Koek Wouter,
Khanal Mandar,
France Charles P.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a413-c
Subject(s) - baclofen , phencyclidine , pharmacology , dizocilpine , catalepsy , nmda receptor , ketamine , agonist , psychology , medicine , neuroscience , dopamine , receptor , haloperidol
Gamma‐hydroxybutyrate (GHB) is used to treat narcolepsy, and is abused as a “club drug”. GHB is often abused together with other “club drugs”, such as the N‐methyl‐d‐aspartate (NMDA) 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 GABA B agonist baclofen from saline. In the PCP‐trained rats, the dose‐response (DR) curve for PCP's discriminative stimulus (DS) effects 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 GHB's baclofen‐like DS effects 2.2‐fold to the left. In contrast, PCP did not shift baclofen's DR curve. These results suggest that NMDA antagonists potentiate not only the cataleptic effects of high doses of GHB, but also the DS effects of low doses, PCP and GHB enhance each others DS effects, and this mutual enhancement may be specific for GHB, because it did not occur with PCP and baclofen. These findings suggest that NMDA antagonists such as PCP and ketamine may potentiate the subjective effects of GHB in humans. The results are further evidence that glutamatergic systems modulate effects of drugs of abuse. Supported by USPHS Grants DA15692 (W.K.) and DA17918 (C.P.F.)