Article ; Online: Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission.
Proceedings of the National Academy of Sciences of the United States of America
2021 Volume 118, Issue 5
Abstract: Clinical studies have reported that the psychedelic lysergic acid diethylamide (LSD) enhances empathy and social behavior (SB) in humans, but its mechanism of action remains elusive. Using a multidisciplinary approach including in vivo electrophysiology, ...
| Abstract | Clinical studies have reported that the psychedelic lysergic acid diethylamide (LSD) enhances empathy and social behavior (SB) in humans, but its mechanism of action remains elusive. Using a multidisciplinary approach including in vivo electrophysiology, optogenetics, behavioral paradigms, and molecular biology, the effects of LSD on SB and glutamatergic neurotransmission in the medial prefrontal cortex (mPFC) were studied in male mice. Acute LSD (30 μg/kg) injection failed to increase SB. However, repeated LSD (30 μg/kg, once a day, for 7 days) administration promotes SB, without eliciting antidepressant/anxiolytic-like effects. Optogenetic inhibition of mPFC excitatory neurons dramatically inhibits social interaction and nullifies the prosocial effect of LSD. LSD potentiates the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and 5-HT |
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| MeSH term(s) | Animals ; Avoidance Learning/drug effects ; Behavior, Animal/drug effects ; Lysergic Acid Diethylamide/pharmacology ; Male ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice, Inbred C57BL ; Neurons/drug effects ; Neurons/metabolism ; Optogenetics ; Phosphorylation/drug effects ; Prefrontal Cortex/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Pyramidal Cells/drug effects ; Pyramidal Cells/metabolism ; Receptors, AMPA/agonists ; Receptors, AMPA/metabolism ; Receptors, N-Methyl-D-Aspartate/agonists ; Receptors, N-Methyl-D-Aspartate/metabolism ; Receptors, Serotonin/metabolism ; Social Behavior ; Synapses/drug effects ; Synapses/metabolism ; Synaptic Transmission/drug effects ; TOR Serine-Threonine Kinases/metabolism ; Mice | |||||
| Chemical Substances | Receptors, AMPA ; Receptors, N-Methyl-D-Aspartate ; Receptors, Serotonin ; Lysergic Acid Diethylamide (8NA5SWF92O) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) | |||||
| Language | English | |||||
| Publishing date | 2021-01-25 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 209104-5 | |||||
| ISSN | 1091-6490 ; 0027-8424 | |||||
| ISSN (online) | 1091-6490 | |||||
| ISSN | 0027-8424 | |||||
| DOI | 10.1073/pnas.2020705118 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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