Chronic treatment with LY341495 decreases 5-HT2A receptor binding and hallucinogenic effects of LSD in mice

NEUROSCIENCE LETTERS

卷:536

Article

Moreno, Jose L.¹  Holloway, Terrell¹  Rayannavar, Vinayak¹  Sealfon, Stuart C.^2,3,4  Gonzalez-Maeso, Javier^1,2,3 

[1] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA

[2] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA

[3] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY 10029 USA

[4] Mt Sinai Sch Med, Ctr Translat Syst Biol, New York, NY 10029 USA

关键词: Serotonin 5-HT2A receptor;    Metabotropic glutamate 2 (mGlu2) receptor;    Lysergic acid diethylamide (LSD);    LY341495;    G protein-coupled receptor (GPCR);    Schizophrenia;   

DOI  :  10.1016/j.neulet.2012.12.053

来源: Elsevier

【 摘 要 】

Hallucinogenic drugs, such as lysergic acid diethylarnide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT2A receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24 mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5 mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [H-3]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT2A agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT2A receptor-dependent hallucinogenic effects of LSD. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

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