Date of Award

Summer 7-26-2018

Degree Type

Thesis

Degree Name

Master of Science in Integrative Biology (MSIB)

Department

Biology

Committee Chair/First Advisor

Susan Smith

Major Professor

Lisa Ganser

Second Committee Member

Martin Hudson

Abstract

Driven by the communication of dopamine, the vertebrate reward system has been evolutionarily conserved to maintain survival and optimize fitness. The neural circuits governing this system integrate sensory stimuli to produce appropriate, self-preserving responses that underlie experience-based learning. In the most primitive vertebrates, dopamine release in neuronal circuits drives homeostatic behaviors, such as seeking nutrients, finding a mate, or avoiding danger. From agnathans to mammals, dopaminergic synthesis and signaling genes and molecules, along with neuronal pathways and reward system-based behaviors, remain highly conserved. Dopamine signaling proteins include two classes of metabotropic G-Protein Receptor Coupled Dopamine Receptors, D1-like (DRD1) and D2-like (DRD2). DRD1 stimulate the neuron by upregulating adenylate cyclase activity, while DRD2 inhibits neurons by blocking or down-regulating adenylate cyclase. Though greatly conserved, the reward system can be hijacked by chemicals that trigger the release of dopamine. Drugs of abuse, like amphetamines, for instance, increase dopamine availability to trigger reward circuits, leading to addiction behaviors. The mechanisms by which amphetamines stimulate dopamine release among reward neurons and the addiction behaviors expressed have not yet been modeled and correlated in zebrafish, a viable translational model for studying drug addiction. In the present study, addictive behaviors in zebrafish were elicited after fish were exposed to amphetamines through a condition place preference paradigm. After the conditioning period, amphetamine-treated fish spent significantly more time in an experimental tank compartment that was paired with amphetamine exposure (p = 0.0031). Likewise, THC (p = 0.0393) and the anesthetic, MS222 (p = 0.0290) significantly affected time spent in the non-preferred tank compartment after conditioning. Amphetamine-treated fish also displayed unique and heightened anxiety and vigilance behaviors. These behaviors and the influence of amphetamines on conditioned learning are likely stimulated by the increased expression of DRD1 receptors measured in dopaminergic brain areas in the fish compared to controls. These data support the hypothesis that drugs of abuse like amphetamines trigger the communication of dopamine among reward circuit neurons.

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