Influence of PCPA and MDMA (ecstasy) on physiology, development and behavior in Drosophila melanogaster

Para-chlorophenylalanine (PCPA) and MDMA ('ecstasy') each delay development and reduce movement and feeding in larval fruit flies. PCPA blocks serotonin synthesis and MDMA depletes serotonin in mammalian neurons, so the experiments targeted the serotonergic system. PCPA lowered serotonin and dopamine levels in the larval brain, while MDMA did not reduce serotonin. The central nervous system remained sensitive to externally applied serotonin, but PCPA reduced that sensitivity, suggesting serotonin receptor regulation depends on neural activity. MDMA enhanced the central response to serotonin, indicating a possible agonist action or release of serotonin from neurons. Heart responses to serotonin were unchanged by either drug.

Study at a glance

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.