Inactivation of the Dopamine Transporter Reveals Essential Roles of Dopamine in the Control of Locomotion, Psychostimulant Response, and Pituitary Function

https://doi.org/10.1016/S1054-3589(08)60722-XGet rights and content

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DA is involved in the control of movement, cognition, and affect, as well as neuroendocrine secretion. In the periphery, DA regulates pituitary and parathyroid hormone synthesis and secretion. The role of the DAT in the CNS has been largely inferred from the clinical and psychosocial effects of drugs such as antidepressants and psychostimulants. These drugs interfere with the function of DAT. However, the involvement of DAT in the peripheral as well as the hypothalamic-neuroendocrine actions of DA has remained more enigmatic. The findings suggest that, in the absence of DA uptake, (-/-) DAT animals are hyperdopaminergic. In an attempt to examine whether this hyperdopaminergic behavioral phenotype was reflected at the biochemical level, several parameters were examined. Messenger RNAs for genes that are normally under dopaminergic control, such as prepro-enkephalin and dynorphin, showed variations indicative of increased dopaminergic tone. Similarly mRNAs for pre- and postsynaptic D2 dopamine receptors, as well as striatal D1 receptors, were markedly (>50%) diminished. In the absence of a functional DAT, the (-/-) DAT mice have undergone major adaptive changes in their biochemical and neurochemical mediators of dopaminergic transmission in an attempt to dampen the presumed increased DA signal.

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