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Sepsis has become one of the most frequent causes of mortality in intensive care centres. So far, there is no effective pharmacotherapy that can prevent or improve the neurological consequences and enhance survival. The goal of this study is to investigate the neuroprotective effect of lemon balm (Melissa officinalis) on behavioural dysfunctions produced in sepsis-surviving rats. Adult male rats were subjected to caecal ligation and puncture and the control animals were submitted to the sham operation. Lemon balm ethanolic extract or saline, given orally, was administered for one week after surgery procedures. Locomotion, anxiety, depressive behaviour and memory were investigated. In the elevated plus-maze (EPM), the percentage of open arm entries and open arm time was very significant in the animals treated with lemon balm extract, similar to the diazepam response in sham-operated and sepsis-surviving rats. Locomotion in open field tests and the enclosed arm entries in the EPM were not significantly altered by treatments. In the forced swimming (FS) test, the extract was effective at reducing the immobility time as that demonstrated by fluoxetine. In the step-down inhibitory avoidance test, the extract eased the effects on memory of sepsis-surviving animals. Collectively, these results demonstrate that lemon balm ethanolic extract could be used for the prevention of cognitive and mood-related deficits that may be associated with sepsis sequelae. Key words: Anxiety, depression, locomotion, Melissa officinalis, memory.

Sepsis and its complications are important causes of mortality in intensive care units and sepsis survivors may present long-term cognitive and emotional impairments, including memory deficits and anxiety symptoms. In the present study, we investigated whether repeated nicotine administration can affect the behavioral changes in sepsis-surviving rats. Male Wistar rats were divided in two groups: sham-operated and experimental sepsis induced by cecal ligation and puncture (CLP). The animals were injected subcutaneously with nicotine (0.1 mg/kg) or vehicle once a day during 1 week before and/or 1 week after sepsis induction. Thirty minutes after the last administration (i.e., 7 days after surgery), the animals were tested in the open field, elevated plus-maze and step-down inhibitory avoidance tasks. The repeated nicotine treatment did not affect the survival rate in the sepsis group (50%). Moreover, no significant changes on locomotor activity were observed in the sepsis group while the treatment with nicotine during 1 week after surgery reduced the locomotion of sepsis-surviving rats in the open field. It is important to note that both schedules of nicotine treatment (prior and/or after CLP) improved the sepsis-induced anxiogenic-like responses. Interestingly, nicotine was able to improve short- and long-term inhibitory avoidance memory impairments, observed in sepsis survivors, only when administered during 2 consecutive weeks (i.e., prior and after CLP). Taken together, these results indicate that repeated nicotine administration does not alter the survival rate in rats submitted to CLP and provide new evidence that nicotine can improve long-lasting memory impairments and anxiogenic-like responses in sepsis-surviving animals.

Objective: To analyse the behavioral effects of Melissa officinalis extract in rats following acute or subacute treatment. Materials and Methods: The behavioral effects of an acute or subacute (10-day course) orally administered M. officinalis (MO; 0, 30, 100 or 300 mg/kg) ethanol extract were evaluated in male and female Wistar rats in elevated plus-maze (EPM), forced swimming (FS) and open field (OF) tests. The effects of diazepam (DZP; 1 mg/kg) and fluoxetine (FXT; 10 mg/kg) were also assessed. Results: In the EPM test, the percentage of open arm entries and open arm times of both males and females given the subacute M. officinalis ethanol extract were significantly higher than those of the vehicle-treated animals but were at levels similar to those observed in the DZP group, regardless of the treatment length. In the FS test, immobility duration was significantly lower in both males and females treated with the plant extract when compared to vehicle-treated counterparts. A 10-day treatment with FXT induced the same antidepressant response, regardless of gender, and was more effective than the M. officinalis extract. Male and female rats demonstrated distinct gender profiles, and treatment × gender interactions were observed. Locomotion in the EPM and OF tests was not significantly altered by treatments. Conclusion: The potential psychoactive properties of M. officinalis may provide a unique pharmacological alternative for certain psychiatric disorders; however, the efficacy appears to be dependent on both gender and administration length.