Evidence on the impairing effects of Ayahuasca on fear memory reconsolidation.

RATIONALE: To uncover whether psychedelic drugs attenuate fear memory responses would advance the development of better psychedelic-based treatments for posttraumatic stress disorder (PTSD). Ayahuasca (AYA), a psychedelic brew containing indolamine N, N-dimethyltryptamine (DMT) and ß-carbolines, facilitates fear extinction and improves neural plasticity. Upon retrieval, fear memory undergoes labilization and reconsolidation; however, the effects of AYA on this memory stabilization phase are unknown. OBJECTIVES: We aimed to investigate the effects of AYA treatment on fear memory reconsolidation. METHODS: Fear-conditioned Wistar rats received AYA (60, 120, or 240 mg/kg) or H2O orally via gavage o.g. 20 min before, immediately, or 3 h after a short retrieval session. Analysis of AYA through liquid chromatography-tandem mass spectrometry was used to determine the content of DMT and ß-carbolines in AYA. RESULTS: AYA impaired fear memory reconsolidation when given 20 min before or 3 h after memory retrieval, with the dose of 60 mg/kg being effective at both moments. This dose of AYA was devoid of anxiolytic effect. Importantly, during retrieval, AYA did not change fear expression. The lack of retrieval abolished the reconsolidation impairing effect of AYA. The effects of AYA treatment 20 min before or 3 h after memory retrieval lasted at least 22 days, suggesting no spontaneous recovery of fear memory. Fear memory impairments induced by AYA treatment, at both moments, do not show reinstatement. CONCLUSIONS: Our findings support the view that a low dose of AYA treatment impairs early and late stages of memory reconsolidation instead of facilitating fear extinction.

Antinociceptive and anti-inflammatory effects of Costus spicatus in experimental animals.

CONTEXT: Costus spicatus Swartz (Costaceae), commonly called "cana-do-brejo'" in Brazil's northeast, is a medicinal plant found in wet coastal forests. In folk medicine an infusion of the aerial parts is taken to treat inflammation and pain. OBJECTIVE: The methanol extract obtained from the leaves of Costus spicatus (MECs) was evaluated for antinociceptive and anti-inflammatory activities. METHODS: Analgesic and anti-inflammatory activities were studied by measuring nociception through acetic acid, formalin, and hot-plate tests, while inflammation was induced by carrageenan. All experiments were conducted with experimental animals. RESULTS AND DISCUSSION: Following oral administration, MECs (100, 200, and 400 mg/kg) significantly reduced the number of writhes (52.8, 43.1, and 55.3%, respectively) in the writhing test and the number of paw licks during phase 1 (61.9, 54.1, and 92.1%) and phase 2 (62.5, 82.9, and 98.1%, all doses) during the formalin test when compared to the control group animals. The reaction time during the hot-plate test was increased significantly and was dose-dependent, whereas pretreatment with naloxone rigorously reduced the analgesic potential of MECs, which suggested participation of the opioid system in the modulation of pain induced by MECs. Such results were unlikely to be provoked by motor abnormality, as MECs-treated mice did not exhibit any performance alteration during the Rota-rod test. The administration of 200 and 400 mg/ kg (i.p.) of MECs exhibited an anti-inflammatory effect during the carrageenan test, which was based on interference with inflammatory mediator synthesis. CONCLUSION: We conclude that MECs has antinociceptive and anti-inflammatory activities in rodents.