Upregulation of (+)-7-Hydroxy-N,N-di-n-[3H]Propyl-2-Aminotetralin Binding Following Intracerebroventricular Administration of a Nitric Oxide Generator |
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Authors: | Wallace David R. Booze Rosemarie M. |
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Affiliation: | (1) College of Osteopathic Medicine, Department of Pharmacology and Physiology, Oklahoma State University, Tulsa, Oklahoma, 74107-1898;(2) College of Osteopathic Medicine, Department of Pharmacology and Physiology, Oklahoma State University, Tulsa, Oklahoma, 74107-1898;(3) Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, 40536-0084 |
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Abstract: | Nitric oxide modulation of dopamine D2 and D3 receptor binding was examined using [125I]epidepride (D2) and (+)7-hydroxy-N,N-di-n-[3H]propyl-2-aminotetralin([3H](+)-7-OH-DPAT, D3). Nitric oxide, generated by i.c.v. injection of S-nitroso-N-acetyl-penicillamine (SNAP; 5 g or 10 g), significantly increased the density of [3H](+)-7-OH-DPAT binding sites (39% and 134%, respectively) in the striatum 24 hours post-injection in the absence of Gpp(NH)p, representing an upregulation of either D3, receptors or high affinity D2 receptors. In the presence of 10 M Gpp(NH)p, D3 receptor upregulation was maintained in both the 5 g (increased 35%) and 10 g SNAP (increased 44%) groups. [3H](+)-7-OH-DPAT binding was reduced in both striatum and nucleus accumbens in the presence of 10 M Gpp(NH)p compared to binding in the absence of Gpp(NH)p, suggesting an upregulation of D3 receptors. Administration of SNAP did not alter total specific [125I]epidepride binding in either brain region. These data suggest that; 1) D3 receptor density is modified following nitric oxide generation, and 2) the density of high affinity D2 receptors identified by [3H](+)-7-OH-DPAT increases in the striatum, but decreases in the nucleus accumbens. |
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Keywords: | Striatum nucleus accumbens nitric oxide guanylate cyclase |
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