Adolescent Antidepressant Treatment and Drug Reward

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Until relatively recently, to think about childhood depression was almost impossible. Now we not only know that major depressive disorder exists in children and adolescents, but that it is also a common condition. It is estimated that youngsters who suffer from depression often develop conduct and anxiety disorders, 20-25% develop substance abuse disorder, and that 5-10% are likely to complete suicide within 15 years of their initial episode of major depression. This has resulted in disproportionate increases in the prevalence of antidepressant drugs prescribed to youths under 20 years of age. Despite increases in antidepressant use, little is known about the short- and long-term behavioral and neuronal adaptations resulting from antidepressant treatment during the juvenile period. Thus, the major objective of this research proposal is to study the behavioral responses to antidepressant treatment during the adolescent period in rats, and to assess the long-term behavioral consequences of this early antidepressant treatment later in adulthood. First, this objective(s) will be accomplished with experiments designed to evaluate the effectiveness of selective serotonin inhibitors (SSRI), using the Forced Swim Test paradigm, in adolescent and adult rats. Second, once effective doses are determined, experiments assessing the long-term behavioral consequences of SSRIs treatment on reward-dependent behaviors will follow. This will be done with experiments assessing animals' sensitivity to a) natural rewards (sucrose and novelty-induced), and b) sensitivity to drugs of abuse (e.g. cocaine) using the Conditioned Place Preference paradigm. Thus, the immediate overall goal of the proposed studies is to begin "closing the gap" in our basic knowledge of the long-term behavioral effects of early life antidepressant treatment, and their interaction with brain circuits that modulate reward-dependent behaviors later in life. The long-term goal is to setup the stage for follow up experiments that will further examine the behavioral consequences of long-term psychotropic treatments during early life, and to assess the biochemical integrity of reward pathways, using basic protein biochemistry analysis, after such treatments. Data obtained from these experiments will improve our understanding of how psychotropics drugs affect developing brain resulting in neural adaptations to influence behavior later in life, especially vulnerability to drugs of abuse.