Date of Award

2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Neuroscience

First Advisor

Loretta M. Flanagan-Cato

Abstract

Sodium appetite is a reliable and robust behavior displayed by a broad range of species. Despite its key role in survival, the biological basis of this behavior remains undefined. The goal of this thesis is to elucidate the cellular signaling and neural circuitry underlying sodium appetite. More specifically, I focus on the central actions of the hormones aldosterone and Angiotensin II (AngII) in eliciting this crucial ingestive behavior. First, I tested the hypothesis that a signaling protein downstream of the AngII receptor, Mitogen Activated Protein Kinase (MAPK), underlies sodium appetite induced by endogenous AngII. I demonstrated through both behavioral pharmacology and protein expression that sodium appetite requires MAPK activation but thirst does not. Next, I tested the hypothesis that aldosterone and AngII potentiate sodium appetite through inactivation of an inhibitory signal. Using functional neuroanatomy and reversible lesions, I revealed that behavioral cooperativity between aldosterone and AngII involves the alleviation of an inhibitory oxytocin signal relayed from the paraventricular nucleus of the hypothalamus to the organum vasculosum lateral terminalis. Finally, I tested the hypothesis that an increase in motivation for sodium is associated with an increase in mesolimbic dopamine activity. Using a progressive ratio schedule of reinforcement and functional neuroanatomy, I discovered that the combination of AngII and aldosterone induces a selective drive for sodium, which is associated with an increase in neural activity and markers of dopamine synthesis in the ventral tegmental area and nucleus accumbens. Together, these findings demonstrate that MAPK signaling is important for AngII-induced sodium appetite, and potentiation of sodium appetite by aldosterone plus AngII requires both inhibition of oxytocin secretion and activation of downstream mesolimbic circuitry.

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