Ovariectomy Results in Variable Changes in Nociception, Mood and Depression in Adult Female Rats

Abstract

Decline in the ovarian hormones with menopause may influence somatosensory, cognitive, and affective processing. The present study investigated whether hormonal depletion alters the nociceptive, depressive-like and learning behaviors in experimental rats after ovariectomy (OVX), a common method to deplete animals of their gonadal hormones. OVX rats developed thermal hyperalgesia in proximal and distal tail that was established 2 weeks after OVX and lasted the 7 weeks of the experiment. A robust mechanical allodynia was also occurred at 5 weeks after OVX. In the 5th week after OVX, dilute formalin (5%)-induced nociceptive responses (such as elevating and licking or biting) during the second phase were significantly increased as compared to intact and sham-OVX females. However, chronic constriction injury (CCI) of the sciatic nerve-induced mechanical allodynia did not differ as hormonal status (e.g. OVX and ovarian intact). Using formalin-induced conditioned place avoidance (F-CPA), which is believed to reflect the pain-related negative emotion, we further found that OVX significantly attenuated F-CPA scores but did not alter electric foot-shock-induced CPA (S-CPA). In the open field and forced swimming test, there was an increase in depressive-like behaviors in OVX rats. There was no detectable impairment of spatial performance by Morris water maze task in OVX rats up to 5 weeks after surgery. Estrogen replacement retrieved OVX-induced nociceptive hypersensitivity and depressive-like behaviors. This is the first study to investigate the impacts of ovarian removal on nociceptive perception, negative emotion, depressive-like behaviors and spatial learning in adult female rats in a uniform and standard way.

Selective activation of estrogen receptors α and β: Implications for depressive-like phenotypes in female mice exposed to chronic unpredictable stress

“…Irrespective of CUS condition, ovariectomy increased passive-coping behaviour in the tail suspension test, and under non-CUS conditions, this effect was prevented by E2, DPN, and PPT treatments. This finding is consistent with previous reports showing that ovarian hormone deprivation alone increases depressive-like behaviour in both rats and mice, at least in the short term (Bekku and Yoshimura, 2005;Li et al, 2014). Importantly, our findings implicate both ERα and β in mediating the effects of estradiol to promote active-coping behaviour under non-stress conditions.…”

Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats

“…Ovarian hormones not only play an important role in reproductive behavior, but also involve in emotion, memory, neuronal survival and perception of somatosensory stimuli 3,11 . On the other hand, mood disorders in women have been reported to be more common than men 12 .…”

“…This fact has been attributed to hormonal changes in premenstrual and postpartum periods which have also been confirmed in hypoestrogenic conditions occurred during medical surgery or menopause 13 . Using FST and tail suspension tests, an increase in immobility time and a decrease in active behaviors were reported 2-4 weeks after ovariectomy in both rats and mice which were partially reduced by estradiol injection 11,14 . In the present study, the ovariectomized rats showed higher immobility and lower active times compared to sham operated ones when the animals were examined in FST.…”

Spontaneous failure of the estrous cycle induces anxiogenic-related behaviors in middle-aged female mice

“…Little literature information is specifically aimed to investigate the influence of menopausal transition on mood-related behaviors in rodents; generally, the effect of spontaneous and surgical-induced menopause on mood-related behaviors is the main focus of preclinical studies. For instance, in forced swimming and tail suspension tests, increases in immobility time which were thought to be indicative of depressive-like behaviors have been observed some weeks after ovariectomy in both rats and mice [39][40][41][42][43][44]. Previously, our research group showed that 20-month old females (which are in post-menopause) are more depressed than adult female rats when assessed in the forced swimming test [34].…”