1. Procedures are described to prepare nutritionally adequate rat milk-substitutes by modifying commercially available processed cow's milk, rich in
carbohydrate and low in
protein and fat compared with rat's milk. 2. Premilk formulas, prepared as intermediates in the preparation of rat milk-substitutes, are rich in
protein but low in their concentration of fat,
carbohydrate, and minerals when compared with rat's milk. 3. Premilks were supplemented with
lactose,
vitamins, minerals, fat as oil mixtures, certain
amino acids and other constituents to yield rat milk-substitutes which resemble the known composition of rat's milk in their properties and composition. 4. Detailed analyses of the milk-substitutes show them to be comparable to rat's milk in energy content, pH, osmolarity, the concentration of the macronutrients, fat,
protein and
carbohydrate, and the major minerals. 5. Rat pups were artificially reared from postnatal day 4 or 5 until days 16-18 by fitting them with gastric cannulas through which the milk-substitutes could be infused automatically. 6. The nutritional impact of the milk-substitutes was assessed by a comparison of growth and metabolic characteristics for artificially reared rats with age-matched sucking rats reared by their mother. 7. Indices which were taken to be appropriate included (a)
body-weight gain; (b) the concentration in blood of
protein,
amino acids,
ketone bodies,
carnitine,
glucose,
galactose,
lactate,
insulin, and the
electrolytes calcium,
sodium,
potassium and
chloride; (c) the turnover of
glucose and
3-hydroxybutyrate; (d) the concentration in brain of
protein,
cholesterol, cerebroside sulphate and the activities of the
enzymes pyruvate dehydrogenase (EC 1.2.4.1), 3-oxo-acid-CoA
transferase (EC 2.8.3.5) and
acetoacetyl-CoA ligase (EC 6.2.1.16). 8. The studies suggest that milk-substitutes approximating to rat's milk in composition promote acceptable metabolism in the artificially reared rat pup.