Brain Crosstalk in Puberty and Adolescence

Abstract

Adolescence is a developmental stage that is associated with increased risk-taking, novelty-seeking and greater vulnerability to peer pressure. Given this, it is perhaps not surprising that adolescence is also a time that is associated with drug experimentation. In some cases, drug experimentation progresses to drug dependence, a state commonly referred to as addiction. As the adolescent brain is still developing, how does drug dependence impact brain development? Imaging studies suggest that cocaine dependence is associated with abnormalities in brain structure in humans. However, it is unclear whether these differences in brain structure predispose an individual to drug use or are a result of cocaine’s action on the brain. We have addressed this issue by studying the impact of chronic cocaine exposure on brain structure and drug-related behavior in mice. In our studies, mice were exposed to cocaine at two developmental time periods: adolescence (27–46 days-old) and young adulthood (60–79 days-old). Following 30 days of abstinence, either fixed brain T2 weighted MRIs were acquired on a 7T scanner at 32 μm isotropic voxel dimensions or mice were assessed for sensitization to the locomotor stimulant effects of cocaine. Three automated techniques (deformation-based morphometry, striatum shape analysis and cortical thickness assessment) were used to identify population differences in brain structure in cocaine vs. saline-exposed mice. We found that cocaine induced changes in brain structure, and these were most pronounced in mice exposed to cocaine during adolescence. Many of these changes occurred in brain regions previously implicated in addiction, including the nucleus accumbens, striatum, insular cortex, orbital frontal cortex and medial forebrain bundle. Furthermore, exposure to the same cocaine regimen caused sensitization to the locomotor stimulant effects of cocaine, and these effects were again more pronounced in mice exposed to cocaine during adolescence. These results suggest that altered brain structure following one month of abstinence may contribute to these persistent drug-related behaviors and may identify cocaine exposure as the cause of these morphological changes.