Role of the posterodorsal medial amygdala in predator odour stress-induced puberty delay in female rats.

Xiao Feng Li,Kevin T O'Byrne,Michel Pilot,Daniel A Adekunbi,Hussah M Alobaid,Shengyun Li,Stafford L Lightman

doi:10.1111/jne.12719

Abstract

Puberty onset is influenced by various factors, including psychosocial stress. The present study investigated cat‐odour stress on puberty onset and oestrous cyclicity in rats. Female weanling rats were exposed to either soiled cat litter or fresh unused litter for 10 consecutive days. Following vaginal opening (VO), rats were smeared for 14 days to determine oestrous cyclicity. Anxiety‐like behaviour was assessed using standard anxiety tests. Brains were collected to determine corticotrophin‐releasing factor (CRF), CRF receptor 1 (CRF‐R1) and CRF receptor 2 (CRF‐R2) mRNA in the paraventricular nucleus (PVN), as well as the central nucleus of the amygdala (CEA) and the medial nucleus of the amygdala (MEA). Cat odour delayed VO and first oestrus, disrupted oestrous cycles and caused anxiogenic responses. Cat odour elicited increased CRF mRNA expression in the PVN but not in the CeA. CRF‐R1 and CRF‐R2 mRNA levels in the PVN and CeA were unaffected by cat odour; however, CRF‐R1 mRNA levels were decreased in the MeA. The role of CRF signalling in the MeA, particularly its posterodorsal subnucleus (MePD), with respect to pubertal timing was directly examined by unilateral intra‐MePD administration of CRF (0.2 nmol day‐1 for 14 days) via an osmotic mini‐pump from postnatal day 24 and was shown to delay VO and first oestrus. These data suggest that CRF signalling in the MePD may be associated with predator odour‐induced puberty delay.

Highlights

The maturation of the hypothalamic-pituitary gonadal (HPG) axis which drives the onset of puberty is influenced by numerous intrinsic and extrinsic factors including stress, especially psychosocial stress which can either delay or advance puberty in both humans and experimental animals (1-3)
The present study demonstrates that chronic exposure to cat odour delays puberty onset, disrupts oestrous cyclicity and elicits fear responses in female Sprague-Dawley rats
These phenotypic and behavioural outcomes were accompanied by increased CRF expression in the paraventricular nucleus (PVN) and decreased CRF-R1 mRNA level in the MeA

Summary

Introduction

The maturation of the hypothalamic-pituitary gonadal (HPG) axis which drives the onset of puberty is influenced by numerous intrinsic and extrinsic factors including stress, especially psychosocial stress which can either delay or advance puberty in both humans and experimental animals (1-3). A major site for CRF expression is the hypothalamic paraventricular nucleus (PVN), the central driver of the hypothalamic-pituitary-adrenal (HPA) axis, lesion studies suggest that PVN CRF may not be critical in stress-induced disturbance of the HPG axis (5). Besides being involved in the stress response, both CRF and the amygdala are importantly involved in fear and anxiety (9, 10). CRF in the amygdala may play a role in disorders linked to both excessive stress, fear and anxiety, such as post-traumatic stress disorder (PTSD) (10)

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Conclusion