Chronic mild stress induces differential depression-like symptoms and c-Fos and 5HT1A protein levels in high-anxiety female Long Evans rats

Abstract

Depression and anxiety disorders overlap in clinical populations, suggesting common mechanisms that may be further investigated in reliable animal models. We used filial 8 female Long-Evans rats bred for high (HAn; n = 19) and low anxiety (LAn)-like behavior (n = 21) to assess forced swim test mobility strategies and chronic mild stress (CMS)-induced depression-like symptoms. We measured (1) weight, (2) fur piloerection, (3) sweet food consumption, (4) grooming behavior, and (5) circulating estradiol (E2). One month after CMS terminated and following a terminal forced swim test, brains were processed for immunohistochemistry targeting c-Fos and serotonin 1 A receptor (5-HT1AR) protein in the paraventricular nucleus (PVN) of the hypothalamus. HAn female rats showed increased anxiety-like behavior (i.e., lower open to closed arm ratios, increased closed arm entries), more swimming (i.e., mobility), and less floating (i.e., immobility) behavior in the forced swim test. Overall, HAn females weighed less than their LAn counterparts. After chronic mild stress, HAn lines displayed even greater mobility and consumed fewer Froot Loops™. Fur and grooming analyses indicated no significant differences in mean counts across experimental groups. One month after CMS, cycling E2 concentrations (pg/ml) did not differ between HAn and LAn animals. Elevated c-Fos and 5-HT1AR expression were observed in the PVN, where HAn CMS rats expressed the most c-Fos and 5-HT1AR immunoreactivity. In summary, outbred HAn rats show robust anxiety-like behavior, exhibit more mobility in the forced swim test, and are more sensitive to chronic mild stress-induced grooming and decline in palatable food ingestion.