Chronic hyponatremia impairs memory in rats: effects of vasopressin antagonist tolvaptan.
The effects of stable chronic hyponatremia on the central nervous system are largely unknown, clinically, or in experimental animals. The aim of this study was to identify and characterize these effects in rats. Tolvaptan, a vasopressin V(2) receptor antagonist, was used to correct hyponatremia and determine any potential benefits of such treatment in this condition. Stable chronic hyponatremia was induced by combination of the continuous vasopressin V(2) receptor stimulation and liquid food intake. The hyponatremic rats did not exhibit significant changes in general symptoms or neurological functions assessed by modified Irwin's method, or in motor function assessed by the rotarod test. In passive avoidance test, however, rats with moderate and severe hyponatremia had significantly reduced step-through latency, indicating impairment in memory. This reduced step-through latency was improved by the treatment of tolvaptan (0.25-8 mg/kg daily doses), a vasopressin V(2) receptor antagonist. This improvement is associated with normalization of plasma sodium concentrations in hyponatremic rats. In conclusion, these data suggest that chronic hyponatremia may impair memory, and treatments that normalize sodium level, such as vasopressin V(2) receptor antagonists, may be beneficial to patients with hyponatremia.
Miyazaki
Toshiki
T
First Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd, Kawauchi-cho, Tokushima, Japan. t_miyazaki@research.otsuka.co.jp
Ohmoto
Koji
K
Hirose
Tsuyoshi
T
Fujiki
Hiroyuki
H
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001362:Avoidance Learning; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D001834:Body Water; D001921:Brain; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage; D007010:Hyponatremia / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology*; D009043:Motor Activity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000097:blood; D000077602:Tolvaptan
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D017483:Receptors, Vasopressin; D000077602:Tolvaptan; D012964:Sodium; D003894:Deamino Arginine Vasopressin