2015 • Physical and LIfe Sciences
Estrogen-Dopamine Interactions During Extinction Learning in Female Rats
Lead Presenter: Ronan Talty
Women are twice as likely as men to develop Post Traumatic Stress Disorder (PTSD), but the neurobiological factors underlying this discrepancy are mostly unknown. In preclinical studies using fear conditioning and extinction paradigms, female rats with low estrogen levels exhibit impaired extinction retrieval. We have shown previously that estrogen can modulate dopaminergic transmission to rescue extinction retrieval impairments, suggesting that the estrogen-dopamine interactions may be important during extinction learning. However, the physiological effects of estrogen on dopamine (DA) transmission during fear extinction are unknown. Intact female Long-Evans rats underwent a 2-day fear conditioning and extinction learning paradigm. Rats were then grouped according to estrous phase during extinction learning (day 2). All rats showed comparable freezing levels during fear conditioning and extinction regardless of estrous phase. We performed immunohistochemistry for c-fos expression in prelimbic and infralimbic regions of the medial prefrontal cortex during extinction learning, and found that low-estradiol rats had increased activation of infralimbic neurons compared to high-estradiol rats. We also used immunohistochemistry for c-fos and tyrosine hydroylase (TH) to quantify activation of DA neurons in the ventral tegmental area (VTA). Despite equal numbers of total TH + cells in all groups, high-estradiol rats had a greater percentage of c-fos labeled TH + cells in the VTA than low-estradiol rats.