Eating disorders (EDs) are some of the most severe psychiatric conditions that primarily affect the female sex. Women are significantly more likely than men to suffer from EDs and the female bias in ED risk is one of the largest in all of psychiatry. The prevalence rates for EDs in women are on par with several other major psychiatric disorders, but the severity of medical complications and psychiatric co-morbidities inherent to EDs are far worse than most other psychiatric conditions. For this reason, uncovering the specific biological and neural mechanisms that contribute to ED risk, development, and exacerbation is crucial. To that end, functional MRI (fMRI) in women with EDs has become a common modality for investigating the neurobiological variables inherent to EDs, as fMRI techniques anatomically localize critical “hot spots” of apparently abnormal neural activity that may be associated with eating pathology. Indeed, several lines of working using fMRI in women with EDs have demonstrated aberrant activity within prefrontal cortex (PFC) circuitry specifically during tasks that engage behavioral control mechanisms, particularly in women with EDs associated with the core, maladaptive symptom of binge eating. These data provide compelling evidence that dysfunctional PFC-mediated regulation over food intake may underlie eating pathology, namely binge eating. To study the role of the PFC in the context of eating pathology, animal models are valuable tools as the rodent medial PFC (mPFC) has several executive functions that are analogous to the human PFC. In addition, the rodent mPFC exerts behavioral control over palatable food (PF) intake, at least in male rodents: the mPFC acts as a behavioral “brake” or limit over excessive PF intake. Thus, pathological eating behaviors, specifically binge eating, may be due in large part to deficient, mPFC-mediated behavioral control over PF intake. However, complete understanding of the underlying neural mechanisms by which the mPFC may contribute to binge eating is still lacking. Specifically, few studies, to date, have investigated whether the mPFC is implicated in binge eating using 1) a clinically-relevant rodent model of binge eating, or 2) female rodents. To that end, the goal of this dissertation was to identify the functional significance of the mPFC to PF intake and to binge eating using a well-validated animal model of binge eating proneness in female rodents. The experiments within this dissertation test the hypothesis that mPFC-mediated control over PF intake is weaker in female rats that are prone to binge eating. The first aim revealed different patterns of activation in the mPFC of binge eating prone (BEP) vs. binge eating resistant (BER) female rats, following exposure to PF. The second aim used double-label immunohistochemistry to identify that a vast majority of PF-activated neurons within the mPFC are excitatory, glutamatergic projection neurons, and that fewer excitatory neurons are engaged by PF in BEPs as compared to BERs. Using reversible, pharmacological inactivation of the mPFC, the third aim demonstrated that the mPFC of female rats indeed serves as a behavioral limit over excessive PF intake, but that the strength of the mPFC-mediated “brake” on PF intake is weaker in BEP rats as compared to BER rats. Thus, the experiments within this dissertation identify not only the cellular players within the mPFC that contribute to PF intake but also the functional significance of the mPFC to binge eating in the female sex.
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