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Stress encompasses reactions to stimuli that promote negative and positive effects on cognitive functions, such as learning and memory processes. Herein, we investigate the effect of restraint stress on learning, memory, anxiety levels and locomotor activity of male and female mice. We used the plus-maze discriminative avoidance task (PMDAT), a behavioral task based on the innate exploratory response of rodents to new environments. Moreover, this task is used to simultaneously evaluate learning, memory, anxiety-like behavior and locomotor activity. Male and female mice were tested after repeated daily restraint stress (4 h/day for 3 days). The results showed stress-induced deficits on aversive memory retrieval only in female mice, suggesting a sexual dimorphism on memory acquisition. Furthermore, stressed females exhibited increased anxiety-like behavior and decreased exploratory behavior. Plasma corticosterone levels were similarly increased by restraint stress in both sexes, suggesting that the behavioral outcome was not related to hormonal secretion. Our findings corroborate previous studies, showing a sexually dimorphic effect of restraint stress on cognition. In addition, our study suggests that stress-related acquisition deficit may be the consequence of elevated emotional response in females.

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Serotonin (5-HT) reuptake inhibitors, such as fluoxetine, are the most prescribed antidepressant for maternal depression. In this sense, it exposes mothers and the brains of infants to increased modulatory and trophic effects of serotonergic neurotransmission. 5-HT promotes essential brain changes throughout its development, which include neuron migration, differentiation and organisation of neural circuitries related to emotional, cognitive and circadian behavior. Early exposure to the SSRIs induces long-term effects on behavioral and neural serotonergic signalisation. We have aimed to evaluate the circadian rhythm of locomotor activity and the neurochemical content, neuropeptide Y (NPY) and 5-HT in three brain areas: intergeniculate leaflet (IGL), suprachiasmatic nuclei (SCN) and raphe nuclei (RN), at two zeitgebers (ZT6 and ZT18), in male and female rat's offspring early exposed (developmental period GD13-GD21) to fluoxetine (20 mg/kg). First, we have conducted daily records of the locomotor activity rhythm using activity sensors coupled to individual cages over 4 weeks. We have lastly evaluated the immunoreactivity of NPY in both SCN and IGL, as well the 5-HT expression in the dorsal and medial RN. In summary, our results showed that (1) prenatal fluoxetine affects phase entrainment of the rest/activity rhythm at ZT6 and ZT18, more in male than female specimens, and (2) modulates the NPY and 5-HT expression. Here, we show male rats are more susceptible to phase entrainment and the NPY and 5-HT misexpression compared to female ones. The sex differences induced by early exposure to fluoxetine in both the circadian rhythm of locomotor activity and the neurochemical expression into SCN, IGL and midbrain raphe are an important highlight in the present work. Thus, our results may help to improve the knowledge on neurobiological mechanisms of circadian rhythms and are relevant to understanding the "broken brains" and behavioral abnormalities of offspring early exposed to antidepressants.

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A growing body of evidence demonstrates that estrogen and corticosterone (CORT) impact on cognition and emotion. On the one hand, ovarian hormones may have beneficial effects on several neurophysiological processes, including memory. On the other hand, chronic exposure to stressful conditions has negative effects on brain structures related to learning and memory. In the present study, we used the plus-maze discriminative avoidance task (PMDAT) to evaluate the influence of endogenous variations of sex hormones and exposure to different types of prolonged stressors on learning, memory, anxiety-like behavior and locomotion. Female Wistar rats were submitted to seven consecutive days of restraint stress (4 h/day), overcrowding (18 h/day) or social isolation (18 h/day) and tested in different phases of the estrous cycle. The main results showed that: (1) neither stress conditions nor estrous cycle modified PMDAT acquisition; (2) restraint stress and social isolation induced memory impairments; (3) this impairment was observed particularly in females in metestrus/diestrus; (4) stressed females in estrus displayed less risk assessment behavior, suggesting reduced anxiety-like behavior; (5) restraint stress and social isolation, but not overcrowding, elevated corticosterone levels. Taken together, our findings suggest that the phase of the estrous cycle is an important modulatory factor of the cognitive processing disrupted by stress in female rats. Negative effects were observed in metestrus/diestrus, indicating that the peak of sex hormones may protect females against stress-induced memory impairment.

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Passiflora cincinnata Masters is a Brazilian native species of passionflower. This genus is known in the American continent folk medicine for its diuretic and analgesic properties. Nevertheless, few studies investigated possible biological effects of P. cincinnata extracts. Further, evidence of antioxidant actions encourages the investigation of possible neuroprotective effects in animal models of neurodegenerative diseases. This study investigates the effect of the P. cincinnata ethanolic extract (PAS) on mice submitted to a progressive model of Parkinson's disease (PD) induced by reserpine. Male (6-month-old) mice received reserpine (0.1 mg/kg, s.c.), every other day, for 40 days, with or without a concomitant treatment with daily injections of PAS (25 mg/kg, i.p.). Catalepsy, open field, oral movements, and plus-maze discriminative avoidance evaluations were performed across treatment, and immunohistochemistry for tyrosine hydroxylase was conducted at the end. The results showed that PAS treatment delayed the onset of motor impairments and prevented the occurrence of increased catalepsy behavior in the premotor phase. However, PAS administration did not modify reserpine-induced cognitive impairments. Moreover, PAS prevented the decrease in tyrosine hydroxylase immunostaining in the substantia nigra pars compacta (SNpc) induced by reserpine. Taken together, our results suggested that PAS exerted a neuroprotective effect in a progressive model of PD.