The use of stimulant medications for attention deficit hyperactivity, which is diagnosed in 2 - 6% of children in North America, has almost tripled since 1990 The increased usage presumably stems from wider recognition of this disorder, as well as the expanding knowledge that such stimulant medication continues to be effective over years, well into adulthood, without known production of adverse side effects There is yet no consensus on the mechanisms of the commonly used anti-hyperactivity medications, amphetamine and methylphenidate Both drugs promote psychomotor slowing of hyperactive children and adults, yet both raise extracellular dopamine levels Paradoxically, elevation of dopamine enhances motor activity, and forms the basis of medications for Parkinson's disease This apparent paradox is the focus of the pilot study The objective of the research is to investigate a novel hypothesis, that a the normal pulsatile supply of dopamine, with a broad range of c oncen trations, results in a different pattern of receptor availability and trafficking than a constant and high supply of the neurotransmitter, which may result with anti-hyperactivity medications To pursue this research, we are cloning the monkey D1 and D2 dopamine receptors and will investigate this hypothesis with the receptor expressed in vitro and in vivo with imaging PUBLICATION Seeman P and Madras BK Anti-hyperactivity medication methylphenidate and amphetamine Mol Psychiatry 3 386-396, 1998
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