The role of estrogen in the onset and performance of plucking behavior in a mouse model of trichotillomania

Trichotillomania (TTM), or repetitive hair-plucking, is one of the most common disorders in women, yet very little is known about the biological causes and mechanisms of the disorder. Barbering is a similar hair-plucking behavior in mice that is a validated model for TTM. Previous studies show a correlation between changes in reproductive physiology and the onset/exacerbation of symptoms in both humans and mice, suggesting that reproductive hormones play a role in TTM but this has yet to be confirmed. Past research has also implicated dopamine, serotonin, and the endogenous opiates dynorphin and enkephalin in TTM and other Abnormal Repetitive Behaviors. These chemicals play a strong role in the corticostriatal loops throughout the brain; at least two of these loops (motor and dorsolateral prefrontal loops) have been implicated in TTM. Therefore, we tested whether estrogen plays a role in barbering, and if so, how it influences dopamine/serotonin/opiate interactions and their regulation of the corticostriatal loops. We predicted that high estrogen doses would delay the onset and prevalence of barbering. We also predicted differences in catecholamines, opiates, and estrogen between groups such that barbers would show underactivity of the indirect pathway as well as downregulation of serotonin and its metabolite, 5-HIAA. Finally, we predicted that estrogen-treated non-barbers would show levels of dopamine and/or enkephalin similar to that of non-barbering controls. In order to test our hypotheses, we gave twenty-eight-day-old C57BL/6J female mice with intact ovaries five acute 17β-estradiol benzoate injections four days apart and then we monitored the onset and severity of barbering compared to vehicle-treated females. We also examined brain chemistry to determine differences in levels of catecholamines (dopamine, serotonin, epinephrine, and norepinephrine) and their metabolites (DOPAC, HVA, 5-HIAA), opiates (dynorphin and enkephalin), and 17β-estradiol between groups. Estrogen decreased barbering prevalence. Brain chemistry pin-pointed a barbering fingerprint indicative of impulsivity and downregulation of the indirect pathway (brain circuitry responsible for the inhibition of competing motor programs). Finally, mice that put on the most weight during the time period of injections (i.e. puberty) were the most likely to barber and results suggest that weight gain is an indicator of a system gone awry rather than a direct cause of barbering. Most importantly, estrogen appears to have increased the threshold for the amount of weight gain required in order to become a barber. Overall, our results begin to shed light on an underlying mechanism and implicate disruption within the energy regulation pathways, suggesting that hormonal regulation of adiposity signals is critical in determining whether hair-pulling occurs in predisposed individuals