Year of Publication

2007

Document Type

Dissertation

College

Arts and Sciences

Department

Biology

First Advisor

Robin Lewis Cooper

Abstract

The regulation and modulation of the serotonergic system is clinically significant in humans. Abnormally low levels of serotonin can result in depression and conditions like panic disorder, obsessive-compulsive disorder, social anxiety disorder, sudden infant death syndrome, and eating disorders. The mechanistic role of serotonin (5-HT) on the neural circuits related with these diseases is not definitively known. Drosophila is a simple model system that provides an advantage over vertebrates to modify genetically and for electrophysiological studies on identifiable cells. In this organism the sensory-CNS-motor circuit is modulated by 5-HT, octopamine (OA), and dopamine (DA), which gives one insight that these neuromodulators are playing a role in central neuronal circuits. The role of 5-HT in the behavior and development of Drosophila melanogaster larvae is being studied. p-CPA (para-chlorophenylalanine) blocks the synthesis of 5-HT by inhibiting tryptophan hydroxylase. The development, behavior and physiology in 3rd instar larvae are affected after feeding this drug. MDMA (3,4 methylenedioxyamphetamine), an analog of methamphetamine is a drug of abuse that has been shown to cause depletion of 5-HT from nerve terminals. It causes the 5-HT transporter to work in reverse. Thus, a dumping of 5-HT results. In Drosophila 3rd instar larva development, physiology and behavior are effected when MDMA is fed throughout their development period. Also at the fly neuromuscular junction, (NMJ) MDMA is causing more evoked vesicular release of glutamate from the presynaptic nerve terminal. Also using anti-sense expression of the 5-HT2dro receptor, role of 5-HT and one of its receptors is studied on development, physiology and behavior. Knock down of 5-HT2dro resulted in developmental delay. Physiology and behavior were also abnormal in these animals.

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