Chronic treatment with LY341495 decreases 5-HT_2A receptor binding and hallucinogenic effects of LSD in mice

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• 作者：José ; L. Moreno^a ; Terrell Holloway^a ; Vinayak Rayannavar^a ; Stuart C. Sealfon^b ; ^c ; ^d ; Javier Gonzá ; lez-Maeso^a ; ^b ; ^c ; ^{Javier.Maeso@mssm.edu}
• 关键词：Serotonin 5-HT2A receptor ; Metabotropic glutamate 2 (mGlu2) receptor ; Lysergic acid diethylamide (LSD) ; LY341495 ; G protein-coupled receptor (GPCR) ; Schizophrenia
• 刊名：Neuroscience Letters
• 出版年：2013
• 出版时间：1 March, 2013
• 年：2013
• 卷：536
• 期：Complete
• 页码：69-73
• 全文大小：310 K

文摘

Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT_2A 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 [³H]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-HT_2A 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-HT_2A receptor-dependent hallucinogenic effects of LSD.