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Adolescent drug exposure and its consequences for the development of drug addiction and related cognitive disorders in adulthood.

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Samenvatting van de aanvraag

Adolescence is a critical stage of brain development during which many people come into contact with socially accepted drugs. Of the top three substances used by teenagers, alcohol, nicotine and marijuana, relatively little is known about their effects on brain development. About 80% of the Dutch youth younger than 17 years of age regularly use socially accepted drugs. From human population data is accumulating that adolescent drug use increases the risk for developing psychiatric disorders, e.g. cognitive and anxiety disorders and drug abuse in later life. The long-term effects of early drug exposure in human adolescents are the result of a complex interaction of genetic make-up, drug exposure and environment. Individual differences in susceptibility combined with diverse social interactions have precluded causal studies into the interaction and contribution of each of these factors to the development of cognitive and behavioral impairments in later life. Since human cohorts always suffer from uncontrolled gene environment interaction histories, human studies have failed to assess whether affected brain development during adolescence causally contributes to adult behavior. For the same reason, it is unclear whether there is a causal relation between socially accepted drug use during adolescence and the development of cognitive disorders in adult life. Therefore, in order to accurately address the acute and long-term effects of these substances we will use animal models that allow control over gene-environment interactions. First, we ask the question whether and how adolescent drug use gives rise to cognitive disorders. Second, we aim to delineate the neuronal mechanisms that might make the adolescent period a unique time window for drug-induced changes in brain plasticity, leading to motivational, cognitive and emotional disturbances in adulthood. Using a multidisciplinary preclinical approach at the behavioral, neurophysiological and molecular level our proposed studies intend to reveal the critical changes that occur in the adolescent stage of the brain, and thereafter, as a consequence of alcohol, nicotine or cannabis exposure. In particular, we will evaluate the long-term consequences of adolescent drug exposure on cognitive functioning using advanced animal models designed to measure changes in motivation, attention, impulsivity and anxiety. Animal models have been shown to closely mimic aspects of human behavior in cognition and addiction. Our proposal aims to yield (i) evidence for the existence of a critical window of vulnerability in adolescence causally contributing to adult behavior, (ii) the discovery of novel targets for the treatment of drug-related disorders (iii) an assessment of the risk of early exposure of ?social drugs? to cognitive dysfunction in adulthood.

Onderwerpen

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Projectnummer:
91206148
Looptijd: 100%
Looptijd: 100 %
2006
2011
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
Prof. dr. G. Smit
Verantwoordelijke organisatie:
Vrije Universiteit Amsterdam