dolescent Exposure to Cannabinoids Induces ong-Lasting Changes in the Response to Drugs of buse of Rat Midbrain Dopamine Neurons

ackground: Recent studies have raised concerns about subtle long-lasting neurobiological changes that might be triggered by xposure to Cannabis derivatives, especially in a critical phase of brain maturation, such as puberty. The mesolimbic dopamine (DA) ystem, involved in the processing of drug-induced reward, is a locus of action of cannabinoids and endocannabinoids. Thus, we ompared the effects of repeated cannabinoid administration in adolescent and adult rats on DA neuronal functions and responses o drugs of abuse. ethods: Single-unit extracellular recordings from antidromically identified mesoaccumbens DA neurons and from their target cells n the nucleus accumbens were carried out in urethane-anesthetized rats. Animals were pretreated during adolescence or adulthood, or 3 days, with the cannabinoid agonist WIN55212.2 (WIN) or vehicle and allowed a 2-week interval. esults: In cannabinoid-administered rats, DA neurons were significantly less responsive to the stimulating action of WIN, regardless f the age of pretreatment; however, in the adolescent group, but not in the adult, long-lasting cross-tolerance developed to morphine, ocaine, and amphetamine. onclusions: Our study suggests that an enduring form of neuronal adaptation occurs in DA neurons after subchronic cannabinoid ntake at a young age, affecting subsequent responses to drugs of abuse.