Nerve growth factor attenuates hippocampal cholinergic deficits and operant learning impairment in rats with...

In the present study we investigated whether continuous intraventricular nerve growth factor (NGF) infusion could ameliorate hippocampal cholinergic deficits and learning impairment following entorhinal cortex lesions. Rats with such lesions received continuous intraventricular infusions of NGF or vehicle. Unlesioned rats with a sham operation were studied as controls. After learning sessions, a dialysis probe was implanted in the CA3 hippocampal region. In addition, brain sections were stained for synaptophysin immunoreactivity. In rats undergoing surgical procedures similar to those in the behavioral study, brains were processed for acetylcholinesterase (AChE) histochemistry. NGF-treated rats showed partial amelioration of lesion-associated hippocampal acetylcholine (ACh) efflux deficits and fixed-interval schedule learning impairment compared with vehicle-treated rats. Histochemical, immunohistologic, and microdensitometric analyses confirmed greater density of AChE-positive fibers and synaptophysin immunoreactivity in CA3, in NGF-treated rats relative to vehicle-treated rats, although not as great as in sham-operation rats, indicating partial recovery in NGF-treated rats. These results suggest that enhanced performance of the learning task with NGF treatment was related to improved hippocampal cholinergic function: specifically, increased cholinergic neurotransmission resulting from NGF effects on cholinergic neurons and presynaptic terminals.