Involvement of the 5-HT2A receptor in the regulation of hippocampal-dependent learning and neurogenesis

Selective serotonin uptake inhibitors (SSRIs) are known to stimulate the production of new neurons in the hippocampus (HPC) by increasing synaptic concentration of serotonin (5-HT). The delay in the appearance of antidepressant effects corresponds to the time required to generate new neurons. However, it is not clear which of the many serotonergic receptors in the HPC are responsible for the enhanced neurogenesis. The current study evaluated the effects of the acute and chronic administration of 5HT2A agonists psilocybin and 251-NBMeO and the 5HT2A/C antagonist ketanserin on hippocampal neurogenesis. To investigate the effects of acute drug administration mice received a single injection of varying doses of psilocybin, 251-NBMeO, ketanserin or saline followed by i.p. injections of 75 mg/kg bromodeoxyuridine (BrdU) for 4 consecutive days followed by euthanasia two weeks later. For chronic administration 4 injections of psilocybin, ketanserin or saline were administered weekly over the course of one month. On days following drug injections mice received an injection of 75 mg/kg BrdU and were euthanized two weeks after the last drug injection. Unbiased estimates of BrdU+ and