Date of Completion

Spring 4-30-2014

Thesis Advisor(s)

John D. Salamone; Samantha Yohn

Honors Major

Physiology and Neurobiology

Abstract

Mesolimbic dopamine (DA), particularly in the nucleus accumbens, is involved in regulating behavioral activation and effort-related processes. Interference with DA transmission can lead to the production of symptoms such as anergia, psychomotor slowing, and fatigue that are seen in depression and other related disorders. Considerable evidence indicates that interference with accumbens DA effects response allocation in effort related choice procedures, biasing animals towards the lower effort alternative. Previous studies have shown that administration of the vesicular monoamine transporter-2 (VMAT-2) inhibitor tetrabenazine (TBZ) effects response allocation in the FR5/choice procedure causing a decrease in lever pressing and a compensatory increase in chow consumption. The present studies investigated the ability of curcumin to reverse the TBZ-induced shifts in effort-related choice behavior. Curcumin is a natural dietary metabolite, found in turmeric, which has been successfully used in antidepressant screening paradigms. Additionally, human clinical trials have shown the efficacy of curcumin as an adjunct medication. Curcumin modulates levels of neurotransmitters, such as DA, serotonin (5-HT), and to a lesser extent norepinephrine (NE), by acting as an MAO-A/B inhibitor. Curcumin has low bioavailability. The purpose of the current feeding study was to mimic human administration (i.e., tablets) in rodents by studying the ability of rats to ingest food pellets formulated with curcumin. In these studies, different formulations that included the excipient neusilin were offered to rats. Additionally, the present study was to determine if curcumin that was orally administered by ingestion could reverse the effort-related effects of TBZ.

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