TY - JOUR
T1 - Influence of PCPA and MDMA (ecstasy) on physiology, development and behavior in Drosophila melanogaster
AU - Dasari, Sameera
AU - Viele, Kert
AU - Turner, A. Clay
AU - Cooper, Robin L.
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
KW - CNS
KW - Dopamine
KW - Drugs of abuse
KW - Ecstasy
KW - MDMA
KW - PCPA
KW - Synapse
UR - http://www.scopus.com/inward/record.url?scp=34447626327&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34447626327&partnerID=8YFLogxK
U2 - 10.1111/j.1460-9568.2007.05655.x
DO - 10.1111/j.1460-9568.2007.05655.x
M3 - Article
C2 - 17650115
AN - SCOPUS:34447626327
SN - 0953-816X
VL - 26
SP - 424
EP - 438
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 2
ER -