PT  - JOURNAL ARTICLE
AU  - Felipe Augusto Cini
AU  - Isis Ornelas
AU  - Encarni Marcos
AU  - Livia Goto-Silva
AU  - Juliana Nascimento
AU  - Sergio Ruschi
AU  - José Salerno
AU  - Karina Karmirian
AU  - Marcelo Costa
AU  - Eduardo Sequerra
AU  - Dráulio de Araújo
AU  - Luis Fernando Tófoli
AU  - César Rennó-Costa
AU  - Daniel Martins-de-Souza
AU  - Amanda Feilding
AU  - Stevens Rehen
AU  - Sidarta Ribeiro
TI  - d-Lysergic acid diethylamide has major potential as a cognitive enhancer
AID  - 10.1101/866814
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 866814
4099  - http://biorxiv.org/content/early/2019/12/06/866814.short
4100  - http://biorxiv.org/content/early/2019/12/06/866814.full
AB  - Psychedelic agonists of serotonin receptors induce neural plasticity and synaptogenesis, but their potential to enhance learning remains uncharted. Here we show that a single dose of d-LSD, a potent serotonergic agonist, increased novel object preference in young and adult rats several days after treatment. d-LSD alone did not increase preference in old animals, but could rescue it to young levels when followed by a 6-day exposure to enriched environment (EE). Mass spectrometry-based proteomics in human brain organoids treated with d-LSD showed upregulation of proteins from the presynaptic active zone. A computational model of synaptic connectivity in the hippocampus and prefrontal cortex suggests that d-LSD enhances novelty preference by combining local synaptic changes in mnemonic and executive regions, with alterations of long-range synapses. Better pattern separation within EE explained its synergy with d-LSD in rescuing novelty preference in old animals. These results advance the use of d-LSD in cognitive enhancement.