Serotonin is an ancient neurotransmitter found throughout the brain, but its specific functions remain debated. This review argues that stress, especially from danger or existential threats, increases the activity of the 5-HT2A serotonin receptor subtype. This upregulation is proposed as an adaptive mechanism to enhance learning and avoidance of danger by forming associations with environmental cues signaling threat. The system may contribute to PTSD symptoms during life-threatening situations. The drug MDMA, which activates 5-HT2A receptors, has shown success in treating PTSD and is suggested to paradoxically work through these same receptors to alleviate symptoms. The central claim is that serotonin acts as a stress detection and response system.
MDMA has both stimulant and hallucinogen-like effects, and its two isomers, R(−)-MDMA and S(+)-MDMA, produce different behavioral effects: R(−)-MDMA is hallucinogen-like, while S(+)-MDMA is stimulant-like. In this study, mice were trained to discriminate each isomer from a vehicle in a two-lever operant task. Drugs with hallucinogen-like effects (2C-T-7, DPT) and stimulant-like effects (amphetamine, cocaine) were substituted for the training isomer. Results showed efficacy differences within chemical classes and potency differences within behavioral classes, clarifying the complex discriminative stimulus properties of MDMA isomers.