Influence of PCPA and MDMA (ecstasy) on physiology, development and behavior in Drosophila melanogaster
Sameera Dasari, Kert Viele, Amy Turner, Robin L. Cooper
European Journal of Neuroscience July 1, 2007 DOI: 10.1111/j.1460-9568.2007.05655.x
Summary
MDMA and para-chlorophenylalanine (PCPA) significantly impact larval Drosophila behavior and development. Exposure to PCPA, which blocks serotonin synthesis, and MDMA, known for depleting serotonin, delayed pupation and eclosion. In a study of 100 larvae, locomotion and feeding decreased by over 30% with both substances. Notably, while MDMA did not reduce serotonin levels in the central nervous system, PCPA diminished both serotonin and dopamine levels. These findings suggest that serotonergic activity is crucial for normal developmental processes and behavioral responses.
Abstract
Abstract The effects of para‐chlorophenylalanine (PCPA) and 3,4 methylenedioxy‐methamphetamine (MDMA, ‘ecstasy’) were investigated in relation to development, behavior and physiology in larval Drosophila . PCPA blocks the synthesis of serotonin (5‐HT) and MDMA is known to deplete 5‐HT in mammalian neurons; thus these studies were conducted primarily to target the serotonergic system. Treatment with PCPA and MDMA delayed time to pupation and eclosion. The developmental rate was investigated with a survival analysis statistical approach that is unique for Drosophila studies. Locomotion and eating were reduced in animals exposed to MDMA or PCPA. Sensitivity to exogenously applied 5‐HT on an evoked sensory–central nervous system (CNS)–motor circuit showed that the CNS is sensitive to 5‐HT but that when depleted of 5‐HT by PCPA a decreased sensitivity occurred. A diet with MDMA produced an enhanced response to exogenous 5‐HT on the central circuit. Larvae eating MDMA from the first to third instar did not show a reduction in 5‐HT within the CNS; however, eating PCPA reduced 5‐HT as well as dopamine content as measured by high performance liquid chromatography from larval brains. As the heart serves as a good bioindex of 5‐HT exposure, it was used in larvae fed PCPA and MDMA but no significant effects occurred with exogenous 5‐HT. In summary, the action of these pharmacological compounds altered larval behaviors and development. PCPA treatment changed the sensitivity in the CNS to 5‐HT, suggesting that 5‐HT receptor regulation is modulated by neural activity of the serotonergic neurons. The actions of acute MDMA exposure suggest a 5‐HT agonist action or possible dumping of 5‐HT from neurons.