Stress, Drugs and Neuroscience : Neurobiological Effects of Social Stressors and Drug Exposure in Young and Adolescent Rats

Abstract: Experiences early in life or during adolescence modulate neuronal networks in the immature brain and consequently lay the foundation for future susceptibility or resilience towards psychiatric disorders. The objective in this thesis is to understand, in part, how the surrounding environment shapes the brain of a young individual. Three types of negative life events were studied, in an animal model, for their effects on the brain reward system (i.e., endogenous opioids and dopamine) and voluntary drug intake. These were: disruption of maternal care, disruption of interaction with peers, and exposure to drugs. Stress, in the form of maternal separation, altered expression of opioid genes in the dorsal striatum and amygdala, and the response to subsequent alcohol intake on these genes was dependent on early life conditions. Basal levels of endogenous opioids were also dependent on how the animals were housed in early adolescence. Short single housing (30 minutes) caused an acute stress response as evidenced by increased serum corticosterone and nociceptin/orphanin FQ in brain areas associated with stress. A prolonged single housing resulted in a marked decrease of Met-Enk-Arg6-Phe7 (i.e., a marker of enkephalins) in several brain areas. The endogenous opioids were also affected by repeated exposure of ethanol during adolescence; ethanol intoxication increased the accumbal levels of Met-Enk-Arg6-Phe7 and decreased those of β-endorphin. Residual effects of the adolescent ethanol exposure were found in Met-Enk-Arg6-Phe7 levels in the amygdala, ventral tegmental area, and substantia nigra. Furthermore, rats exposed to ethanol as adolescents had alterations in the dopamine dynamics in the dorsal striatum. Both endogenous opioids and dopamine are essential in mediating rewarding properties. Alterations of these systems, caused by environmental disturbances and alcohol exposure, presented herein could explain, in part, the increased susceptibility for alcohol- and substance use disorders later in life.