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Effects of adolescent cannabinoid exposure on the development of mesocorticolimbic dopamine circuitry

Grant number: 19/23286-3
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): March 01, 2020
Effective date (End): February 28, 2021
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Fabio Cardoso Cruz
Grantee:Sheila Antonagi Engi
Supervisor abroad: Joseph Cheer
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Local de pesquisa : University of Maryland, Baltimore (UMB), United States  
Associated to the scholarship:16/18701-3 - Cannabidiol treatment in behaviours related to ethanol addiction: in vitro and in vivo studies, BP.PD

Abstract

Initiation of drug use during adolescence is a strong predictor of both the incidence and severity of addiction throughout the lifespan. Among adolescents, cannabis is the most commonly abused illicit drug, and excessive use of cannabinoids in this population is associated with the development of psychiatric conditions, including drug addiction. Adolescence is a critical period for the refinement and organization of neuronal connectivity, especially within the mesocorticolimbic dopamine circuity. Previous investigations have shown that exposure to high doses of amphetamine in early adolescence (PND21-32) disrupts the development of mesocorticolimbic dopamine connectivity,leading to alterations in cognitive processing and drug seeking in adulthood. Importantly,this effect is mediated by amphetamine-induced downregulation of the guidance cue receptor gene (Dcc) in ventral tegmental area (VTA) dopamine neurons. DCC receptors orchestrate the development of the mesocorticolimbic dopamine system in adolescence by determining the spatiotemporal targeting of dopamine axons to the nucleus accumbens (NAc) and the medial prefrontal cortex (mPFC). Here, we examine whether exposure to the synthetic cannabinoid-1/2 receptor agonist WIN-55,212-2 (WIN) in adolescence regulates Dcc mRNA expression in the VTA and induces, in turn, adult alterations in cocaine-related behaviors and in dopamine function in adulthood - using optical fiber and simultaneous recording of NAc phasic dopamine release by fiber photometry.