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Quantitative autoradiography demonstrates selective modulation of rat brain regional dopamine (D1 and D2) receptor subtypes after chronic manipulation of dietary salt

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Abstract

The effects of chronic dietary sodium chloride (NaCl) consumption on renal function and brain dopamine receptors were studied in adult, male normotensive rats. Compared to rats maintained on the normal NaCl (0.33%) diet, animals maintained on the low NaCl (0%) diet for 4 weeks exhibited significant increases in plasma aldosterone, chloride and changes in urinary electrolyte excretion. In contrast, rats maintained on the high NaCl (8%) diet for 4 weeks demonstrated significant increases in urine volume and urinary sodium, chloride and dopamine excretions and water intake. Rats fed the high NaCl diet displayed a 42–59% decrease (p<0.001–0.05) in D1 binding in the nucleus accumbens (NA), olfactory tubercle (OT) and the striatum (STM), without any effects on D2 binding in these brain regions. Rats maintained on the low NaCl diet also demonstrated decreased D1 binding in the ventral (24%, p<0.02) and lateral (29%, p<0.01) STM, but not in the OT, NA, entopeduncular nucleus and substantia nigra. Rats fed low or high NaCl diets exhibited a 35–180% increase (p<0.01–0.05) in D2 binding in several mid-brain areas (e.g. hypothalamus, thalamus and hippocampus) and hindbrain regions (e.g. superior colliculus and nucleus tractus solitarius) without affecting the D1 binding. These data indicate that chronic modification of dietary salt intake profoundly affects the renal handling of sodium/water excretion and leads to selective up- and/or down-regulation of DA receptor subtypes in different areas of the brain. These findings may have relevance to centrally-mediated hypertension, Parkinson's disease, schizophrenia and other brain disorders involving dopamine and dopamine receptors.

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Author notes

  1. N. A. Sharif

    Present address: Molecular Pharmacology Unit, Alcon Laboratories, Inc., (R219), 6201 South Freeway, 76134, Fort Worth, Texas

Authors and Affiliations

  1. Syntex Discovery Research, Institute of Pharmacology, 94303, Palo Alto, California

    N. A. Sharif, J. L. Nunes, R. P. Rosenkranz, R. L. Whiting & R. M. Eglen

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Sharif, N.A., Nunes, J.L., Rosenkranz, R.P. et al. Quantitative autoradiography demonstrates selective modulation of rat brain regional dopamine (D1 and D2) receptor subtypes after chronic manipulation of dietary salt. Neurochem Res 20, 121–128 (1995). https://doi.org/10.1007/BF00970535

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