Chronic treatment with LY341495 decreases 5-HT2A receptor binding and hallucinogenic effects of LSD in mice
José L. Moreno, Terrell Holloway, Vinayak Rayannavar, Stuart C. Sealfon, Javier González-Maeso
Neuroscience Letters January 16, 2013 DOI: 10.1016/j.neulet.2012.12.053 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice (wild-type and mGlu2 knockout) |
| Interventions | LY341495 LSD |
| Dose | LY341495 1.5 mg/kg; LSD 0.24 mg/kg |
| Duration | 21 days |
| Measures | head-twitch behavior, c-fos expression, egr-1 expression, egr-2 expression, [3H]ketanserin binding |
| Topics | LSD Mescaline Psilocybin Serotonin |
| Keywords | Hallucinogen Ketanserin Pharmacology Receptor antagonist 5-HT Receptor Metabotropic receptor Glutamate receptor |
| Citations | 44 |
| Key findings | Chronic treatment with the mGlu2/3 receptor antagonist LY341495 reduced 5-HT(2A) receptor binding and hallucinogenic-like responses to LSD in mice, suggesting that repeated mGlu2 receptor blockade diminishes LSD's effects. |
Abstract
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 (0.24mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [(3)H]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.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 18
- Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years Therapeutic Advances in Psychopharmacology March 18, 2016
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans European Neuropsychopharmacology January 16, 2015
- Psychedelic Drugs in Biomedicine TIPS - Trends in Pharmacological Sciences September 22, 2017
- The current state of research on ayahuasca: A systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging Journal of Psychopharmacology June 11, 2016
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Cites 9
- Serotonin research: contributions to understanding psychoses TIPS - Trends in Pharmacological Sciences August 1, 2008
- Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers Neuropsychopharmacology September 28, 2011
- Agonist-Trafficking and Hallucinogens Current Medicinal Chemistry March 1, 2009
- Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neuroscience Letters January 27, 2011
- Psychedelics and schizophrenia. Trends in Neurosciences April 1, 2009
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