Behavioral and biochemical effects of early postnatal cholinergic lesion in the hippocampus

The effects of early postnatal (PD 8) intracerebroventricular injection of ethylcholine mustard aziridinium ion (AF64A) on development of open-field and cognitive behaviors and cholinergic markers in several brain areas were examined in the rat. The cholinotoxin was bilaterally administered in a dose range of 0.25 to 2.0 nmol. In the open-field tests, the cholinergic lesion caused a dose-dependent increase in activity at 20 days of age, while it resulted in lengthened latency to initiate exploration and decreased rearing activity at adulthood. Hole-board spatial learning was severely inhibited in adult age. The biochemical activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the hippocampus was markedly decreased in a dose-dependent manner, but was unchanged in the neocortex and striatum. Histochemical staining of AChE-positive fibers revealed a severe cholinergic denervation of the granular and pyramidal cell layers of the hippocampus. The results showed that a selective cholinergic deafferentation of the hippocampus at a critical stage of development leads to long-lasting abnormal open-field and spatial learning behaviors.