Clinical and pre-clinical findings point to the critical role of ovarian hormones in modulating anxiety and depressive symptoms in female. However, few studies investigated the effects of long-term ovarian hormones withdrawal on animal behavior. The current study evaluated the behavioral effects of long-term ovariectomy (performed at 3 months of life) in adult (6 months old) and aged (18 months old) rats subjected to the elevated plus-maze and forced swimming tests. A substantial reduction in the time spent in open arms in adult and aged ovariectomized rats was observed compared to intact animal from the same age. A significant increase in the immobility time was observed in aged rats, ovariectomized or not, compared to adult rats. It should be noted that no alterations in the spontaneous locomotion were detected among groups. In addition, a reduction in serum concentrations of 17beta-estradiol was observed in adult ovariectomized and aged sham and ovariectomized rats compared to adult intact animals. Taken together, these findings suggest that anxiety-related behaviors were affected by ovariectomy, but not aging. However, the depressive-like behavior observed in aged rats seems to be much more influenced by senescence than ovarian hormones withdrawal. The presented results are discussed considering the effects of gradual and abrupt reduction of ovarian steroids concentrations, and the influence of aging on behavior of female rats.

Nevirapine (NVP) and efavirenz (EFV) belong to the class of anti-HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), commonly used as part of highly active antiretroviral therapy (HAART). Although the HAART is able to bring down viral load to undetectable levels and restore immune function, their prolonged use causes several adverse effects. It has been demonstrated that both NVP and EFV are able to cross the blood-brain barrier, causing important central nervous system-related side effects. Thus, this study investigated the effects of chronic administration of EFV (10 mg/kg) and NVP (3.3 mg/kg) in mice submitted to two distinct series of experiments, which aimed to evaluate: (1) the emotional behavior (elevated plus-maze, forced swimming, and open-field test) and (2) the cognitive performance (object recognition and inhibitory avoidance test) of mice. Our results demonstrated that EFV, but not NVP, reduced the exploration to open arms in the elevated plus-maze test. Neither NVP nor EFV altered mouse behavior in the forced swimming and open-field tests. Both drugs reduced the recognition index in the object recognition test, but only EFV significantly impaired the aversive memory assessed in the inhibitory avoidance test 24 h after training. In conclusion, our findings point to a genuine anxiogenic-like effect to EFV, since it reduced exploration to open arms of elevated plus-maze test without affecting spontaneous locomotion. Additionally, both drugs impaired recognition memory, while only the treatment with EFV impaired significantly aversive memory.

Clinical findings reveal that middle-aged patients are more susceptible to suffer from psychiatric disorders than older ones. However, little is known about the emotional behavior of aging rodents. This study aimed to investigate behavioral alterations in male middle-aged Wistar rats in the open-field (OF) test (at illuminated and dimly light conditions), elevated plus maze (EPM), forced swimming (FST) and inhibitory avoidance task (IA). In the EPM, middle-aged rats displayed reduced percentages of the time spent in and entries into open arms. The ambulatory activity measured in the OF under dimly light conditions was identical among groups. However, under illuminated conditions, a reduction in the number of crossings was detected in older rats, reinforcing that aged animals display a genuine anxiogenic-like phenotype. Additionally, aged rats showed an increase in the immobility time in the FST, and a reduction in the latency to step down the platform in the IA. A negative correlation was found between the immobility time and latency to step down the platform, suggesting a relationship between depressive-behavior and cognitive impairment in old rats. Altogether, male middle-aged rats are more anxious, depressed, and display aversive memory impairments. These observations contribute to investigate biological mechanisms and therapeutic interventions for geriatric anxiety and depression.