Mineralocorticoid receptor antagonism prevents hedonic deficits induced by a chronic sodium appetite.
Our laboratory has reported that manipulations that provoke a robust sodium appetite (e.g., sodium depletion, deoxycorticosterone acetate) decrease lateral hypothalamic self-stimulation (LHSS) reward if rats are denied access to hypertonic saline solutions. The following studies investigated the interaction between chronic sodium appetite and the renin-angiotensin-aldosterone system on LHSS reward. In Experiment 1, animals treated with the diuretic furosemide (20 mg/kg) when denied access to saline exhibited an increase in the current required to produce 50% of the maximum LHSS response rate (ECu50) 48 hr after extracellular volume depletion. Furosemide-depleted rats that were allowed to drink 0.3 M saline after depletion, or that were treated with the selective mineralocorticoid receptor (MR) antagonist spironolactone, which significantly reduced sodium appetite, did not show ECu50 changes. In Experiment 2 chronic intracerebroventricular administration of the selective MR antagonist RU 28318 (10 microg/microl/hr) prevented decreases in the ECu50 induced by deoxycorticosterone acetate-no salt treatment. We conclude that an unresolved sodium appetite will reduce responding for rewards and that experimental manipulations that reduce sodium appetite (e.g., access to saline or blockade of MR) decrease hedonic deficits.
Morris
Michael J
MJ
Department of Psychology, Integrative Physiology and Pharmacology, and the Cardiovascular Center, The University of Iowa, Iowa City, IA 52242-1407, USA.
Na
Elisa S
ES
Johnson
Alan Kim
AK
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000031:analogs & derivatives; D004347:Drug Interactions; D005665:Furosemide; D007010:Hyponatremia / Q000139:chemically induced / Q000523:psychology*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects* / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D011188:Potassium / Q000097:blood / Q000652:urine; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects* / Q000502:physiology; D012964:Sodium / Q000097:blood / Q000652:urine; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D003900:Desoxycorticosterone; D000450:Aldosterone; C041006:RU 28318; D005665:Furosemide; D002216:Captopril; D012964:Sodium; D012083:Renin; D011188:Potassium