Role of polyamines in experience-dependent brain plasticity.

Enriched experience increases brain growth, neuronal differentiation and learning abilities. Polyamines are modulators of growth and differentiation. We studied the effect of difluoromethylornithine (DFMO, an inhibitor of putrescine synthesis) on brain growth of rats exposed either to a complex or an impoverished environment. In both environmental conditions, DFMO decreased cortical putrescine by 50% and increased spermine by 13%; spermidine remained constant. Cortical RNA was not affected significantly by DFMO but DNA was decreased exclusively in rats exposed to the impoverished environment. Environmental complexity increased cortical weight, RNA and spermidine content. These differences were larger in DFMO-injected rats than in saline controls. Since stimulants such as amphetamines also enhance the environmental effects it was conceivable that DFMO might act as a stimulant. We have measured the effect of DFMO on rats' exploratory activity and found it decreased by the drug. Therefore the enhancing effect of DFMO cannot be explained by its behavioral activity. We propose that DFMO enhances the experience-dependent brain plasticity by facilitating differentiation of neurons.