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Growth, Appetite, Sequence of Pathological Signs and Survival Following the Induction of Rapid, Synchronous Vitamin A Deficiency in the Rat^1,2,

Department of Biochemistry, Faculty of Science, Mahidol University, Rama VI Rd., Bangkok 4, Thailand

Experiments were conducted to determine the sequence and reliability of appearance of key signs of vitamin A deficiency. Rapid and essentially synchronous vitamin A deficiency was induced by the withdrawal of retinoic acid from mature (190–210 g) stringently vitamin A-deficient male rats reared by feeding early growth plateau (60–70 g) vitamin A-deprived rats diets first supplemented with and then lacking in 2 µg retinoic acid per gram diet in repeating 18 day:10 day supplementation: deprivation cycles. Growth was depressed within 1 to 2 days of the withdrawal of retinoic acid whether animals were force-fed or were fed ad libitum. Similar patterns were obtained when animals were fed 5 or 10 µg retinoic acid per gram diet. Appetite was depressed (1–2 days) whether animals were fed 18% casein diets, or were given 10% dextrose drinking solutions only. Decreased food intake was not due to impaired taste function or to poor palatability of the deficient diet. Bilateral electrolytic lesions in the ventromedial nucleus of the hypothalamus or anterior prepyriform cortex failed to prevent or to delay loss of appetite. Supplementation with antibiotics decreased body weight losses in the late stages of deficiency and increased survival time. Other signs of deficiency (days until onset following retinoate withdrawal; percent incidence) were: decreased intestinal goblet cell numbers (2–3; 80), decreased pilocarpine induced salivation (6–8; 80), tracheal metaplasia (6–8; 80), transient periocular porphyria (6–8; 60), altered salivary gland morphology (9–10; 80), decreased stomach emptying in force-fed animals (12; 70), twisting (12; 5) and leg crippling (12; 5). We conclude that the sequence of appearance of individual signs of deficiency following the induction of synchronous vitamin A deficiency is highly reproducible, and that the more general use of synchronously deficient animals would materially assist studies of cause-effect relationships in vitamin A deficiency.

KEY WORDS: • retinoic acid • synchronous vitamin A deficiency • growth • appetite • ventromedial nucleus • prepyriform cortex • taste acuity • survival

¹ Supported in part by U.S. National Institutes of Health Grant No. NIH-AM-11367 and the Faculty of Graduate Studies, Mahidol University.

² Taken in part from a thesis submitted by M.A.A. to the Faculty of Graduate Studies. Mahidol University in partial fulfillment of the requirement for a Ph.D. degree.

³ To whom reprint requests should be addressed.

Manuscript received 8 January 1979.

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