Quantitative autoradiography demonstrates selective modulation of rat brain regional dopamine (D1 and D2) receptor subtypes after chronic manipulation of dietary salt.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Sharif
N A
NA
Institute of Pharmacology, Syntex Discovery Research, Palo Alto, California 94303, USA.
Nunes
J L
JL
Rosenkranz
R P
RP
Whiting
R L
RL
Eglen
R M
RM
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001552:Benzazepines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000652:urine; D007457:Iodine Radioisotopes / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000097:blood; D012982:Sodium, Dietary / Q000494:pharmacology*; D013469:Sulpiride / Q000378:metabolism; D013997:Time Factors
D001552:Benzazepines; D007457:Iodine Radioisotopes; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012982:Sodium, Dietary; D013469:Sulpiride; D012964:Sodium; D004298:Dopamine