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It is possible that the reported effects of early life undernutrition on brain morphology may be due to alterations in mother-infant interactions and not directly to undernutrition. We have investigated this possibility by comparing artificially reared with mother-reared rats. Four groups of black-and-white hooded male rats were reared. These consisted of mother reared control (MRC), mother reared undernourished (MRU), artificially reared control (ARC) and artificially reared undernourished (ARU). Artificially reared rats were raised in isolation away from their mothers from 5 to 21 days of postnatal age. They were fitted with a gastric cannula through which 'milk' was infused automatically. The period of undernutrition lasted from 5 to 25 postnatal days, following which the animals were fed ad libitum until 312 days of age. Rats from each group were then killed by perfusion with buffered 2.5% glutaraldehyde. Pieces of visual cortex from each rat were postfixed in osmium tetroxide and embedded in resin. Stereological procedures at the light and electron microscopical levels were used to estimate the synapse-to-neuron ratios in cortical layers II to IV. Both MRC and ARC rats had about 7000 synapses per neuron. However, this ratio was about 8300 in MRU rats whilst it was only about 5000 in ARU animals. The rearing x nutrition interaction was statistically significant at the 0.1% level. These changes in the synapse-to-neuron ratio were mainly due to alterations in the numerical densities of the synapses rather than that of neurons. These results demonstrate that environmental isolation, as a result of artificial rearing procedures, and concurrent undernutrition during the first three weeks of postnatal life, interact with one another to produce marked morphological changes in the adult rat brain. However, environmental isolation was not, by itself, sufficient to cause permanent changes in interneuronal connectivity.

1. Rat pups were artificially reared (AR) from post-natal day 5 by intermittent gastric infusion. Mother-reared (MR) siblings served as controls. Fourteen measures of body and organ growth were taken at the end of each experiment.2. In Expt 1, two batches of pups were given rats' milk only, obtained by manual expression from anaesthetized dams.3. The first batch, reared to 12 d, grew less well than the MR group, probably because they received too little milk. However, relative to body-weight, organ weights were as great or greater than those of MR pups, except for heart weight. The second batch, given more milk and reared to 20d, showed no deficits in organ or body-weights, but excesses in kidney, gastrocnemius muscle, stomach and caecum weights. There were no losses from 'bloat', a condition of gastrointestinal distention often encountered in artificial rearing with milk substitutes.4. Obtaining rats' milk is extremely labour-intensive and in Expt 2, more economical regimens were devised in which pups were started off on expressed rats' milk and then changed to a milk substitute resembling rats' milk in composition, either abruptly at 12 d or gradually between 8 and 17 d.5. Both regimens were successful, in that there were no losses from bloat and most measures of growth were at least as great as in the MR group. Only heart weight was lower in both AR groups and adrenal weight in the abruptly changed AR group. The weights of the stomach and caecum and the length of the small intestine were all high in both AR groups.6. It is concluded that giving rat pups expressed rats' milk for the first few days of artificial rearing largely avoids the problem of bloat and results in satisfactory growth.

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