Perinatal N(G)-Nitro-L-arginine methyl ester administration decreases anxiety- and depression-like behaviors in adult mice

ABSTRACT Objective: We hypothesized that perinatal manipulations of the nitrergic system would affect adult animal behaviors. Methods: We tested this hypothesis by perinatally administering N(G)-Nitro-L-arginine methyl ester (L-NAME), a non-specific antagonist of nitric oxide synthase for 15 days and assessed anxiety- and depression-like behaviors in adult mice. At 70 days of age, the mice were subjected to a battery of tests consisting of the open-field, light/dark box, forced swim, and tail-flick tests. The tests were performed at two-day intervals, and the order of the tests within the battery was determined according to the progressive invasiveness degree. Results: L-NAME-treated animals exhibited decreased anxiety-like behavior in the light/dark box and open field tests, with no change in locomotor activity. Additionally, they demonstrated decreased depression-like behavior in the forced swim test and no change in pain perception in the tail-flick test. Conclusion: The nitrergic system is possibly involved in neural circuitry development that regulates behaviors since blocking perinatal nitric oxide production decreases anxiety- and depression-like behaviors in adult mice.

Anti-nociceptive and anti-oedematogenic properties of the hydroethanolic extract of Sidastrum micranthum leaves in mice

Sidastrum micranthum (A. St.-Hil.) Fryxell, Malvaceae, grows in the northeastern region of Brazil, where the leaves of this species are traditionally used to treat coughs, bronchitis or asthma. Male Swiss mice (20-22 g) were tested in models of acute pain (acetic acid-induced abdominal writhing, tail flick and formalin test), oedema assessment test (paw oedema test) and model for evaluation of spontaneous motor performance (open field test). The hydroethanolic extract of S. micranthum was administered orally at doses of 50-500 mg/kg. In addition were administered water, vehicle, morphine 5.01 mg/kg (evaluation of pain and motor performance) and dexamethasone 2.25 mg/kg (evaluation of oedema formation). The extract showed a significant effect at all doses in the acetic acid-induced abdominal writhing test and at the second phase of the formalin test, while in the first phase of this test and in the paw oedema test only at the highest dose (500 mg/kg). In the formalin and paw oedema tests, the extract had a potentiation of the anti-nociceptive and anti-inflammatory effects by pretreatment with L-NAME and reduction of the effect by pretreatment with L-arginine. The extract was not toxic after oral administration (LD50 > 2000 mg/kg).

Phytochemical profile and analgesic evaluation of Vitex cymosa leaf extracts

Vitex cymosa Bertero ex Spreng., Lamiaceae, is found in Central and Amazon regions of Brazil, where it is popularly used as antirheumatic. Extracts from the leaves of V. cymosa were tested in analgesia models such as abdominal contortions induced by acetic acid and formalin to test peripheral analgesia; as well as the tail flick and hot plate models, to test spinal and supraspinal analgesia. A significant reduction was observed in the number of contortions with all extracts and in all doses. In the formalin model, a reduction in the second phase (inflammatory) was observed with all extracts, whereas only the n-butanol extract was able to act in the first, neurogenic, phase. In the tail flick model, all extracts increased latency time. Naloxone treatment reverted analgesic effect of all extracts with the exception of the dichloromethane one. All extracts developed peripheral and central analgesic activity. In the hot plate model no antinociceptive effect was observed for all tested extracts. All these results taken together suggest that V. cymosa leaf extracts were able to promote peripheral and central antinociceptive activity mediated by the opioid system.Twenty three substances were isolated and identified in the extracts and include flavonoids (C-glucosyl flavones, flavones and flavonols), triterpene acids from ursane and oleanane types, iridoids (free and glucosides), as well as simple phenols.