2-Hydroxyestradiol enhances binge onset in female rats and reduces prefrontal cortical dopamine in male rats

Abstract

Women are more likely to suffer from a bingeing-related eating disorder, which is surprising, since estradiol reduces meal size and is associated with reduced binge frequency. This apparent contradiction may involve the estradiol metabolite, 2-hydroxyestradiol. We previously reported that female rats had faster escalations in shortening intake during the development of bingeing than did males, but acute administration of 2-hydroxyestradiol increased the intake of vegetable shortening to a greater extent in male rats once bingeing was established. Here, we report two separate studies that follow up these previous findings. In the first, we hypothesized that chronic exposure to 2-hydroxyestradiol would promote escalation of bingeing during binge development in ovariectomized female rats. In the second, we hypothesized that acute exposure to 2-hydroxyestradiol would enhance dopamine signaling in the prefrontal cortex after bingeing was established in male rats. In study 1, non-food-deprived female rats were separated into 3 groups: ovariectomized (OVX) with chronic 2-hydroxyestradiol supplementation (E), OVX with vehicle supplementation (O), and intact with vehicle (I). Each group was given access to an optional source of dietary fat (shortening) on Mon, Wed, and Fri for four weeks. 2-hydroxyestradiol supplementation prevented OVX-induced weight gain and enhanced escalation of shortening intake over the four-week period (ps < 0.05). Additionally, in week 4, rats in the E group ate significantly more shortening than I controls, less chow than either the O or I group, and had a higher shortening to chow ratio than O or I (ps < 0.05). Study 2 indicated that acute injection of 2-hydroxyestradiol abolished shortening-evoked dopamine efflux in the prefrontal cortex of bingeing male rats (p < 0.05). Together, these studies indicate that 2-hydroxyestradiol can exacerbate bingeing as it develops and can suppress dopamine signaling in the prefrontal cortex once bingeing is established.

Cytoplasmic FMR1-Interacting Protein 2 Is a Major Genetic Factor Underlying Binge Eating

“…Female F 2 mice wer more prone to BE ( Fig.2; FigS4A,B )(49-51) which is consistent with human studies(52) and could potentially be explained by the sweetened PF diet(51, 53), neurodevelopmental sex differences in the food reward circuitry and response to PF(54), activational effects of gonadal steroids(50, 52, 55), impulsivity(56), and/or neurobehavioral plasticity that underlies negative reinforcement(57). We did not observe sex differences in PF-CPP in F 2 mice ( Fig.S4C,D ); however, we did observe an increase in freezing episodes in female F 2 mice at 24 h post-BE that was specific to PF training ( Fig.S4F-H ).…”

Casein kinase 1‐epsilon deletion increases mu opioid receptor‐dependent behaviors and binge eating1

“…To account for individual and sex differences in body weight, we quantified SPF consumption as percent body weight. To investigate possible differences in escalation in SPF intake over time, regression analyses were conducted in GraphPad Prism 7.01 (GraphPad Software, La Jolla, CA, USA) as previously reported (Babbs et al ., 2013, Kirkpatrick et al ., 2016). …”

The Trace Amine-Associated Receptor 1 Agonist RO5256390 Blocks Compulsive, Binge-like Eating in Rats

“…Therefore, here it can be speculated that the effects of TAAR1 agonism on food reward may occur through modulation of the dopaminergic terminals in the mPFC. Palatable food consumption activates the reward circuitry and releases dopamine in the mPFC (Babbs et al, 2013;Volkow et al, 2008). In addition, limited access to palatable food results in neuroadaptations in the reward circuitries, which contribute to compulsive overeating (Volkow et al, 2013).…”