title: Influence of PCPA and MDMA (ecstasy) on physiology, development and behavior in Drosophila melanogaster.
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.
authors.affiliation: Department of Biology, 675 Rose Street, University of Kentucky, Lexington, KY 40506-0225, USA.
authors.forename: Sameera
authors.initials: S
authors.lastname: Dasari
authors.forename: Kert
authors.initials: K
authors.lastname: Viele
authors.forename: A Clay
authors.initials: AC
authors.lastname: Turner
authors.forename: Robin L
authors.initials: RL
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004331:Drosophila melanogaster / Q000254:growth & development / Q000502:physiology*; D004594:Electrophysiology; D010134:Fenclonine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007814:Larva; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011679:Pupa; D012701:Serotonin / Q000378:metabolism / Q000502:physiology; D018490:Serotonin Agents / Q000494:pharmacology*
chemical_list: D018490:Serotonin Agents; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D010134:Fenclonine; D004298:Dopamine