It is estimated that 3-9% of all school-age children in the United States meet the diagnostic criteria for attention deficit hyperactivity disorder (ADHD) and the majority of these children are treated with methylphenidate (Ritalin). The percentage of school-age children treated with methylphenidate has increased steadily over the last decade and, in recent years, there has been a sharp increase in the number of preschool children given this compound. Despite the large number of children being treated with methylphenidate, surprisingly little is known about the long-term consequences of this drug. Of particular interest is the question of whether early methylphenidate treatment increases later vulnerability to drugs of abuse, because recent research has indicated that early methylphenidate exposure alters cocaine reinforced behavior. Thus, the goal of the proposed research is to determine the effects of early exposure to methylphenidate on reward mechanisms in young adult rats. Five sets of experiments are planned. In the first two sets of experiments, we will expose rats during the preweanling period (a time roughly analogous to early childhood in humans) to methylphenidate and assess morphine-induced place preference, cocaine self-administration, and novelty- and cocaine-induced locomotor activity in adulthood. In the third set of experiments, we will examine changes in the number and functioning of dopamine D2 receptors after preweanling methylphenidate exposure. D2 receptor functioning will be assessed by measuring adenylyl cyclase activity, G-protein subunits levels (i.e., Gi-alpha and Go-alpha), and NPA-stimulated GTPgammaS binding in the striatum and nucleus accumbens. In the fourth set of experiments, we will determine if route of administration (oral vs. ip) or number of injections per day alters the effects of preweanling methylphenidate exposure on morphine-induced place preference. Finally, in a fifth set of experiments, we will determine if age at drug exposure alters the effects of early methylphenidate exposure on morphine-induced place preference and cocaine-self administration.
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