Modulation of the neuroplasticity produced by cocaine administration in mice by ayahuasca

• Grant number: 19/19011-9
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2020
• End date: October 31, 2022
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Tania Marcourakis
• Grantee: Tania Marcourakis
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cocaine is a psychostimulant alkaloid, being in Brazil and Europe, the second most used illicit drug, with a high potential to induce addiction. Faced with this problem, research on psychedelics has intensified with a focus on the treatment of drug addiction. Psychedelics have a good safety profile, do not induce drug addiction and have low potential to cause tolerance. The most studied psychedelics are LSD, MDMA, psilocybin, ibogaine and, in Brazil, ayahuasca (DMT). Ayahuasca is a decoction used in religious rituals formed by the association of Banisteriopsis caapi stems and Psychotria viridis leaves. Preliminary studies from our group showed that ayahuasca is capable of preventing the expression of cocaine-induced behavioral sensitization. Thus, the aim of the present study is to evaluate the effects of ayahuasca on the modulation of neuroplasticity produced by cocaine administration in C57Bl/6 mice. These changes will be evaluated by immunoblotting of dopaminergic and serotonergic receptors (D1R, D2R, 5-HT1AR and 5-HT2AR) and addiction and neuroplasticity-related proteins (dinorphine, pro-dinorphin, cFos, ”FosB, AP-1, CREB, ERK, BDNF and PKA) in the prefrontal cortex, striatum, and hippocampal. In addition, the immunohistochemical technique will be employed for a broader analysis of the neuroplasticity triggered by the treatment; and electrophysiology to verify neuronal activity-dependent synaptic changes: long-term potentiation (LTP) and long-term depression (LTD) induced by ayahuasca per se in both the cortex and hippocampus. (AU)