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

Dasari, Sameera; Viele, Kert; Turner, Amy; Cooper, Robin L.

doi:10.1111/j.1460-9568.2007.05655.x

Cited by 38 publications

(44 citation statements)

References 90 publications

(153 reference statements)

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“…P>0.05, n = 14 animals). On the other hand, two drugs that acutely increase extracellular 5HT levels by blocking the serotonin transporter [37]–[38], [40], fluoxetine (100 µM) and MDMA (1 mM), decrease locomotion in Drosophila larvae compared to control Canton-S (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

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Serotonin Receptors Expressed in Drosophila Mushroom Bodies Differentially Modulate Larval Locomotion

et al. 2014

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Drosophila melanogaster has been successfully used as a simple model to study the cellular and molecular mechanisms underlying behaviors, including the generation of motor programs. Thus, it has been shown that, as in vertebrates, CNS biogenic amines (BA) including serotonin (5HT) participate in motor control in Drosophila. Several evidence show that BA systems innervate an important association area in the insect brain previously associated to the planning and/or execution of motor programs, the Mushroom Bodies (MB). The main objective of this work is to evaluate the contribution of 5HT and its receptors expressed in MB to motor behavior in fly larva. Locomotion was evaluated using an automated tracking system, in Drosophila larvae (3rd-instar) exposed to drugs that affect the serotonergic neuronal transmission: alpha-methyl-L-dopa, MDMA and fluoxetine. In addition, animals expressing mutations in the 5HT biosynthetic enzymes or in any of the previously identified receptors for this amine (5HT1AR, 5HT1BR, 5HT2R and 5HT7R) were evaluated in their locomotion. Finally, RNAi directed to the Drosophila 5HT receptor transcripts were expressed in MB and the effect of this manipulation on motor behavior was assessed. Data obtained in the mutants and in animals exposed to the serotonergic drugs, suggest that 5HT systems are important regulators of motor programs in fly larvae. Studies carried out in animals pan-neuronally expressing the RNAi for each of the serotonergic receptors, support this idea and further suggest that CNS 5HT pathways play a role in motor control. Moreover, animals expressing an RNAi for 5HT1BR, 5HT2R and 5HT7R in MB show increased motor behavior, while no effect is observed when the RNAi for 5HT1AR is expressed in this region. Thus, our data suggest that CNS 5HT systems are involved in motor control, and that 5HT receptors expressed in MB differentially modulate motor programs in fly larvae.

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Section: Resultsmentioning

confidence: 99%

“…Experiments were carried out as explained above. The concentrations of these drugs were chosen according to the information available in the literature [34]–[38] and preliminary experiments carried in our lab (data not shown). Control animals were treated in the same manner with solvent (water).…”

Section: Methodsmentioning

confidence: 99%

Serotonin Receptors Expressed in Drosophila Mushroom Bodies Differentially Modulate Larval Locomotion

et al. 2014

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“…An excellent resource for protocols on visualization, dissection, and electrophysiological recording from larva heart is a publication from Robin Cooper and the accompanying video tutorial (Cooper et al, 2009). Using these methods, it is possible to easily examine the effects of pharmacological agents on heart function (Dasari and Cooper, 2006;Dasari et al, 2007;Neckameyer et al, 2007). Additional tools to facilitate examination of the heart include GAL4 drivers that can be used to express GFP in the heart, allowing for real-time observation of function with conventional epifluorescence or confocal microscopy (Wu and Sato, 2008;Alayari et al, 2009;Vogler and Ocorr, 2009).…”

Section: Cardiovascularmentioning

confidence: 99%

Human Disease Models inDrosophila melanogasterand the Role of the Fly in Therapeutic Drug Discovery

2011

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“…The general dissection technique and HL3 saline content has been previously reported [22,58]. The HL3 saline was derived from direct measures with ion sensitive electrodes of larval hemolymph.…”

Section: Monitoring Heart Rate In the Dissected Larvamentioning

confidence: 99%

“…In brief, tracheal movement is commonly used to monitor Drosophila larval HR because of the clear contrast of the structures [22,58,59]. Early 3 rd instar larvae were glued ventrally on a glass cover slip using super-glue in such a way that mouth hooks are free to move.…”

Section: Monitoring Heart Rate In the Intact Larvamentioning

confidence: 99%

Roles of the Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase, Plasma Membrane Ca2+-ATPase and Na+/Ca2+ Exchanger in Regulation of Heart Rate in Larval Drosophila~!2010-03-10~!2010-08-13~!2010-08-27~!

Desai-Shah¹,

Papoy²,

Ward³

et al. 2010

TOPHYJ

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Abstract:We investigated the roles of three regulatory proteins that impact [Ca 2+ ] i within cardiac myocytes of Drosophila melanogaster. The NCX (Na + /Ca 2+ exchanger), PMCA (plasma membrane Ca 2+ -ATPase) and SERCA (sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase) were compromised by ionic, pharmacological, mutationalmanipulation, and with a combination of approaches, while heart rate (HR) was monitored. A decrease in SERCA function reduced HR more for intact larva in comparison to a dissected larva. Dissected preparations were used to expose the heart directly to agents. A compromised PMCA also reduced HR; however, attenuated NCX function by low [Na + ] o increased HR. KBR7943, a blocker of Ca 2+ entry via NCX, exposure increased HR. A combined loss of function in all three channels did not show a significant change in HR. The results indicate that NCX and PMCA are important in regulating HR, whereas SERCA does not have as pronounced role for dissected preparations. However, with intact preparations the loss of SERCA function by a mutation does have a significant impact on HR. Pharmacological approaches to alter PMCA and SERCA paralleled the results obtained by ionic and mutational approaches. To further understand the pacemaker activity, intracellular recordings were obtained. Mapping of action-potentials in myocytes revealed that the caudal region of the heart has large amplitude potentials and is likely to contain the pacemaker cells. The Drosophila heart can serve as a genetic model in understanding regulation of ionic currents for pacing cells of various types.

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

Cited by 38 publications

References 90 publications

Serotonin Receptors Expressed in Drosophila Mushroom Bodies Differentially Modulate Larval Locomotion

Serotonin Receptors Expressed in Drosophila Mushroom Bodies Differentially Modulate Larval Locomotion

Human Disease Models inDrosophila melanogasterand the Role of the Fly in Therapeutic Drug Discovery

Roles of the Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase, Plasma Membrane Ca2+-ATPase and Na+/Ca2+ Exchanger in Regulation of Heart Rate in Larval Drosophila~!2010-03-10~!2010-08-13~!2010-08-27~!

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