Antidepressant effect of PT-31, an α2-adrenoceptor agonist, on lipopolysaccharide-induced depressive-like behavior in mice.

Increasing evidence indicates that neuroinflammation, oxidative stress, and neurotrophic factors play a key role in the pathophysiology of major depressive disorder (MDD). In addition, the attenuation of inflammatory response has been considered a putative mechanism for MDD treatment. PT-31 is an imidazolidine derivative and a putative α2-adrenoceptor agonist that has previously demonstrated antinociceptive activity. The present study aimed to investigate the effect of PT-31 on depressive-like behavior and lipopolysaccharide-induced neurochemical changes. To this end, mice received intraperitoneally saline or lipopolysaccharide (600 µg/kg), and 5 h postinjection animals were orally treated with saline, PT-31 (3, 10, and 30 mg/kg), or fluoxetine (30 mg/kg). Mice were subjected to the open field test (OFT) 6 and 24 h after lipopolysaccharide administration and to the tail suspension test (TST) 24 h postlipopolysaccharide. Subsequently, animals were euthanized, and brains were dissected for neurochemical analyses. The administration of lipopolysaccharide-induced sickness- and depressive-like behaviors, besides promoting an increase in myeloperoxidase activity and a reduction in brain-derived neurotrophic factor (BDNF) levels. Noteworthy, PT-31 3 mg/kg attenuated lipopolysaccharide-induced decreased locomotor activity 6 h after lipopolysaccharide in the OFT. All tested doses of PT-31 significantly reduced the immobility time of animals in the TST and attenuated lipopolysaccharide-induced increased myeloperoxidase activity in the cortex of mice. Our results demonstrate that PT-31 ameliorates behavioral changes promoted by lipopolysaccharide in OFT and TST, which is possibly mediated by attenuation of the inflammatory response.

Biological Properties of Aloysia gratissima (Gillies & Hook.) Tronc. (Verbenaceae).

Aloysia gratissima is a plant native to America, with applications in folk medicine for a wide range of diseases, such as bronchial infections, lung disorders, nervous system disorders (depression, anxiety), and inflammatory processes, among others. However, investigations about this species and its biological actions are still scarce. This literature review was carried out using articles published in the past 30 years on the PubMed, SciELO, and Web of Science platforms, with the focus on the method of extraction, chemical composition, and clinical and preclinical studies on the pharmacological properties of A. gratissima. We noticed that the main constituents of A. gratissima are guaiol, pinocamphone, ß-pinene, and 1,8-cineole. Additionally, preclinical studies reveal that A. gratissima extracts present antidepressant, anti-inflammatory, antinociceptive, antibacterial, antifungal, and virucidal effects. The results also demonstrate that there is a greater interest on the part of researchers from 2012 onwards in studying A. gratissima extracts with potential for possible new drugs.