The Effect of Intrafrontal Cortex Injection of Physostigmine on Active Avoidance Learning on the Animal Model of Alzheimer's Disease

Cholinergic neurons of nucleus basalis magnocellularis (NBM) have a key role in learning and memory process. It has been shown that these neurons are degenerated in patients with Alzheimer disease (AD). On the other hand, using the cholinomimetic agents and acetylcholinesterase inhibitors improve cognition in these patients. Some studies have shown that the frontal cortex receives some cholinergic projections from NBM. In the present study, the effect of intrafrontal cortex administration of physostigmine (acetylcholinesterase inhibitor) was investigated on active avoidance learning on the animal model of AD. In this experimental study, NBM was lesioned electricaly in Wistar male rats, (250-300g body weight) for making the animal model of AD. Because the frontal cortex receives cholinergic projections from NBM, different doses of physostigmine (2.5, 5, 7.5 µg/µl) were injected bilaterally into the frontal cortex of lesioned rats 20 minutes before active avoidance learning (8 sessions, 30 steps in each session) in Y-maze. The results showned that active avoidance learning was decreased significantly in NBM-lesioned group. Also intrafrontal cortex injection of phsostigmine (2.5, 5, and 7.5 µg/µl) significantly severed NBM lesion-induced learning deficiency. The findings of this study suggest that the cholinergic projection of NBM to frontal cortex in lesioned animals has a negative role on this type of learning. It seems that other neurotransmitter systems such as glutamate and other afferent projections from different brain areas to frontal cortex probably are involved in this phenomenon.