Impacts of chronic intermittent ethanol vapor and stress exposure on striatal D1 medium spiny neurons: modulation by CB1 cannabinoid receptors

• Grant number: 22/10168-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 01, 2023
• End date: January 31, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Fabio Cardoso Cruz
• Grantee: Cristiane Aparecida Favoretto
• Supervisor: Eric Paul Zorrilla
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: Scripps Research Institute, San Diego, United States
• Associated to the scholarship: 19/24073-3 - Role of cannabinoid CB1 receptors in modulating neural circuits involved in the interaction between maternal separation stress and ethanol intake in mice, BP.PD

Abstract

Repeated ethanol consumption and stress are risk factors associated with the development of ethanol-use disorders, which represent a relevant public health issue that impacts millions of individuals worldwide. The D1 medium spiny neurons (MSNs) in the dorsal striatum are a neuronal subpopulation that has been implicated in responses to drugs and stress. Exposure to ethanol or stress seems to alter the expression levels of cannabinoid CB1 receptors, which participate in the modulation of striatal D1-MSNs activity. Chronic intermittent ethanol (CIE) vapor exposure has been used as a predictive animal model to induce long-term addiction-related behaviors and adaptations in neuronal populations implicated in reward and addiction processes, including the striatal D1-MSNs. Here, we propose evaluating the effects of CIE vapor on the dorsal striatum translatome of D1-MSNs (Experiment 1) and the impacts of exposure to CIE vapor or stress on ethanol intake, D1-MSN activation, and CB1 expression in D1-MSNs in the dorsal striatum (Experiment 2). For this, in Experiment 1, adult male and female Drd1-Cre; H2B-TRAP mice were subjected to 6 cycles of exposure to CIE vapor or Air, intercalated with access to voluntary ethanol intake (two-bottle choice paradigm). In the following, brains were collected, and the dorsal striatum region was dissected. The candidate will work with the collected samples that will be processed by translating ribosomal affinity purification (TRAP) of D1-MSN ribosomes for RNA isolation and sequencing. In Experiment 2, adult male and female Drd1-Cre; H2B-TRAP mice will be subjected to a 3-cycle protocol of exposure to CIE vapor or Air, intercalated with access to voluntary ethanol intake. During the last two cycles of the protocol, mice will be subject or not to predator odor stress immediately before each ethanol intake session. Then, brains will be collected, and the dorsal striatum slices will be processed for RNAscope for labelling c-fos (neuronal activation marker), and CNR1 (codifies for CB1 receptors). (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MORAIS-SILVA, GESSYNGER; FAVORETTO, CRISTIANE APARECIDA; PAGLIUSI, MARCO; LEGATES, TARA A.. Editorial: Advances in the involvement of brain cellular subpopulations and pathways in distress and stress-related disorders. FRONTIERS IN NEUROSCIENCE, v. 17, p. 3-pg., 2023-08-29. (21/13291-0, 20/08363-9, 22/10168-5, 19/24073-3, 20/15216-2)

FAVORETTO, CRISTIANE APARECIDA; PAGLIUSI, MARCO; MORAIS-SILVA, GESSYNGER. Involvement of brain cell phenotypes in stress-vulnerability and resilience. FRONTIERS IN NEUROSCIENCE, v. 17, p. 14-pg., 2023-07-05. (21/13291-0, 20/08363-9, 22/10168-5, 19/24073-3, 20/15216-2)