Catlow, B. J., Song, S., Paredes, D. A., Kirstein, C. L., & Sanchez-Ramos, J.. (2013). Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning. Experimental Brain Research, 228(4), 481–491.

Plain numerical DOI: 10.1007/s00221-013-3579-0
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, Psilocybin induced neurogenesis
Abstract

Drugs that modulate serotonin (5-HT) synaptic concentrations impact neurogenesis and hippocampal (HPC)-dependent learning. The primary objective is to determine the extent to which psilocybin (PSOP) modulates neurogenesis and thereby affects acquisition and extinction of HPC-dependent trace fear conditioning. PSOP, the 5-HT2A agonist 25I-NBMeO and the 5-HT2A/C antagonist ketanserin were administered via an acute intraperitoneal injection to mice. Trace fear conditioning was measured as the amount of time spent immobile in the presence of the conditioned stimulus (CS, auditory tone), trace (silent interval) and post-trace interval over 10 trials. Extinction was determined by the number of trials required to resume mobility during CS, trace and post-trace when the shock was not delivered. Neurogenesis was determined by unbiased counts of cells in the dentate gyrus of the HPC birth-dated with BrdU co-expressing a neuronal marker. Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice. Injection of PSOP, 25I-NBMeO or ketanserin resulted in significant dose-dependent decreases in number of newborn neurons in hippocampus. At the low doses of PSOP that enhanced extinction, neurogenesis was not decreased, but rather tended toward an increase. Extinction of “fear conditioning” may be mediated by actions of the drugs at sites other than hippocampus such as the amygdala, which is known to mediate the perception of fear. Another caveat is that PSOP is not purely selective for 5-HT2A receptors. PSOP facilitates extinction of the classically conditioned fear response, and this, and similar agents, should be explored as potential treatments for post-traumatic stress disorder and related conditions.

Source URL: https://link.springer.com/article/10.1007/s00221-013-3579-0


Abstract

Neurogenesis, or the birth of new neurons, occurs throughout the human life span in the hippocampus, a structural node in the neural circuitry responsible for memory and learning. The process of neurogenesis involves proliferation of neural stem/progenitor cells and their differentiation into mature neurons, followed by integration into hippocampal circuitry. The function of new neurons in the hippocampus is not completely understood. The formation of new synaptic connections (and pruning of synapses) between neurons in the hippocampal dentate gyrus and fibers to and from the cerebral cortex is important in the acquisition of new associations (learning), recall of those associations (memory), and extinction of associations (forgetting). Very likely, the new neurons play a role in encoding temporal aspects of episodic memory. Neurogenesis is influenced by many factors, including physical activity, stress, depression, seizures, irradiation, aging, and a variety of psychoactive drugs. Many psychedelic drugs are shown to have an impact on hippocampal neurogenesis in a dose-dependent manner and to alter some aspects of memory and learning. Drug-induced alterations in hippocampal neurogenesis have been shown to alleviate depression and to have beneficial effects on conditioned fear. In light of abundant preclinical data and the loosening of governmental restrictions on psychedelic drug research, these agents should be explored for their therapeutic potential in depression, posttraumatic stress disorders, and drug dependence.

Source URL: https://www.sciencedirect.com/science/article/pii/B9780128002124000777


, Psilocybin induced neurogenesis
A neuronal (b)rainbow
, Psilocybin induced neurogenesis
BrdU (red), a marker of DNA replication, highlights neurogenesis in the subgranular zone of hippocampal dentate gyrus.
, Psilocybin induced neurogenesis
Rodent dentate gyrus