Methylazoxymethanol microencephaly in rats: neurochemical characterization and behavioral studies with the nootropic oxiracetam.

The administration of methylazoxymethanol (MAM) to pregnant rats induced a marked reduction in the weight of the offspring's brain. This reduction was due to aplasia of the cortex and hippocampus, whose thicknesses were 50% of those of control animals. A significant reduction was also observed in the striatum. This aplasia could be ascribed to the antimitotic effect of MAM, which, when given at gestational day 15, prevented the development of neurons in the three brain areas mentioned. Indeed, we infer here that the total number of GABA-receptor complexes, as measured by [3H]muscimol and [3H]flunitrazepam binding, was reduced to the same degree as was the weight of the cortex. Similarly, total [3H]haloperidol binding sites were reduced in the striatum. From the behavioral point of view, offspring of MAM-treated rats (MAM rats) showed impaired acquisition in the water-maze and pole-climbing tests, indicating that this brain aplasia had disrupted cognitive processes. In contrast, these animals showed normal growth, and grossly their behavior appeared normal. Oxiracetam, a new compound that belongs to the recently described class of nootropic drugs, was able to restore acquisition processes in MAM rats. We propose therefore that MAM rats might become an interesting and quite simple animal model for evaluation of new acquisition-enhancing drugs. Moreover, this model could also be useful to study the neurochemical correlates of cognitive processes.