Adolescent mice exposed to MDMA, cocaine, or both drugs showed lasting changes into adulthood in their response to MDMA. Only those pre-treated with MDMA alone developed a conditioned place preference for a low dose of MDMA. All groups developed preference for a higher dose, but extinction took longer in mice pre-treated with cocaine (46 sessions) or MDMA alone (28 sessions). Preference was reinstated with progressively lower priming doses in mice pre-treated with MDMA or cocaine alone. Early exposure to MDMA or cocaine induces long-lasting changes that modify adult responses to MDMA.
Three novel phenethylamine derivatives—25C-NBF, 25B-NBF, and 25I-NBF—show high affinity and selectivity for the 5-HT2A receptor, with signaling bias toward Gq over β-arrestin pathways similar to serotonin. In mice, they cause moderate head-twitch responses without affecting movement or sensorimotor gating. No rewarding or reinforcing effects were observed, and accumbal dopamine levels in rats remained unchanged. 25C-NBF promotes dendritogenesis, spinogenesis, and increased Bdnf mRNA in vitro and in vivo, reduces despair-like behavior after acute stress, and produces rapid antidepressant effects in a chronic corticosterone model of anhedonia. These findings suggest 25C-NBF may offer a fast-acting antidepressant with no abuse potential or sensorimotor deficits.