Increased mRNA for corticotrophin releasing hormone in the amygdala of Fawn‐hooded rats: A potential animal model of anxiety

Abstract

Compared to the outbred Wistar rat strain, the Fawn-hooded rat strain has several characteristics which suggest that the Fawn-hooded strain is hyperaroused. Fawn-hooded rats exhibit more freezing behavior in response to stress, have an increased preference for alcohol, develop adult onset hypertension, and have elevated urinary catecholamine levels. We used quantitative in situ hybridization to investigate central components of the corticotropin releasing hormone (CRH), arginine vasopressin (AVP) and noradrenergic stress response and arousal systems in these rats. We also measured basal corticosterone levels and adrenal weights to assess tonic hypothalamic-pituitary-adrenal axis activity. Compared to Wistar rats, Fawn-hooded rats had significantly increased CRH mRNA in the central nucleus of the amygdala and reduced CRH mRNA in the paraventricular nucleus of the hypothalamus. Fawn-hooded rats also bad reduced AVP mRNA expression in the parvocellular cells of the hypothalamic paraventricular nucleus. There were no differences between strains in glucocorticoid receptor mRNA in the hippocampus or the paraventricular nucleus or in mineralocorticoid receptor mRNA in the hippocampus. There was also no difference between strains in tyrosine hydroxylase mRNA in the locus ceruleus. Finally, adrenal weights were significantly reduced in the Fawn-hooded rats while basal corticosterone levels were similar in the two strains, which suggests central hypoactivity of the hypothalamic-pituitary-adrenal axis in Fawn-hooded rats compared to Wistar rats. Increased CRH mRNA in the central nucleus of the amygdala and reduced tonic hypothalamic-pituitary-adrenal axis activity may play a role in the unique behavioral and physiological characteristics of Fawn-hooded rats.

Abnormalities of hypothalamic-pituitary-adrenal and hypothalamic-somatotrophic axes in Fawn-Hooded rats

“…Although mRNA for CRF in hypothalamic PVN was found to be normal in FH rats, mRNA for CRF in the CeA was found to be increased in FH rats compared with SD rats. This is in accordance with a previous report comparing FH rats (obtained from the same breeder as the present FH rats) and Wistar rats (11), and suggests that enhanced expression of mRNA for CRF in the CeA is a consistent finding. Whether or not this factor might contribute to the development of hypertension in FH rats remains to be the subject of direct study.…”

“…First, true basal activity of the HPA axis does not appear to be supranormal in FH rats, as the same laboratory that reported basal hypercorticosteronaemia subsequently showed normal corticosterone concentrations (11) -a finding corroborated by our own results (12). Secondly, FH rats showed lower relative adrenal weight and greater relative thymus weight as compared with both Wistar and SD rats (11,12). Thirdly, activity of FH rats in the forced swimming test, which is presumed to evaluate depression-like behaviour (13,14), is dependent on the particular substrain used (15).…”

“…Therefore, there is no evidence for either enhanced adrenocorticotrophic function or altered glucocorticoid negative feedback, the two major endocrine alterations in depression (36), in FH rats. Comparing FH and Wistar rats, no evidence for enhanced pituitaryadrenal function was observed (11). In addition, the activity of our particular substrain of FH rats in the forced swimming test, a putative animal model for the evaluation of depression-like behaviour in rodents (13,14), was found to be greater than that of SD rats in a previous report (12).…”

“…Although high basal corticosterone concentrations had previously been found in FH rats compared with Wistar rats (10), more recent papers, including one from the same laboratory that originally reported hypercorticosteronaemia, have reported normal basal concentrations of ACTH and corticosterone in FH rats, as compared with either Wistar or SD rats (11,12). Therefore, earlier results showing higher than usual concentrations of serum/plasma corticosterone in FH rats could have been due to stress associated with blood sampling.…”

Toxoplasma gondiiinfection, from predation to schizophrenia: can animal behaviour help us understand human behaviour?

“…For instance, Lister-hooded rats are believed to be the most behaviourally similar to wild rats, at least in terms of food-related neophobia (Barnett, 1958;Webster, 2007), whilst Fawn-hooded rats have been shown to exhibit more stressinduced fear (freezing) than Wistar rats and have higher levels of corticotropin-releasing factor (CRF) mRNA in their central amygdala (Altemus et al, 1995). One could perhaps also propose that future T. gondii studies could incorporate the spontaneously hypertensive rat (SHR) model of anxiety, to help further elucidate host from parasite associations in relation to generalized anxiety profiles.…”