Over the past four decades, considerable evidence accumulated from both animal and human studies has suggested that central cholinergic (AChergic) systems are involved in the processes of learning and memory. Pharmacological modulations of the brain's AChergic systems are also known to alter memory function. Anticholinergics, like scopolamine and atropine, may disrupt learning and memory by blocking the M-1 muscarinic receptor subtype (AChR) to induce transient amnesia. However, both oxotremorine, an AChR agonist, and physostigmine, an ACh esterase (AChE) inhibitor, have been shown to facilitate learning and memory and reverse experimentally induced memory deficits. Pharmacological studies, however, cannot adequately explain the role of neural mechanisms responsible for such behavioral deficits. The role of ACh in memory has recently gained interest from a clinical viewpoint since senile dementia of the Alzheimer type (SDAT), a disorder characterized by progressive deterioration of cognitive functions, may be related to degeneration of the AChergic neurons in the forebrain based on the studies that showed a marked decrease in choline acetyltransferase (ChAT) activity in the hippocampus and widespread areas of the cortex in affected patients, and a profound loss of neurons in the NBM. The diffused projection from the NBM along with the relatively compact distribution of the cells of origin and the apparent utilization of ACh as a neurotransmitter by these cells, all provide a foundation by which the relationship between the brain ACh and behavior can be studied from a new research strategy— that is, destruction of the neuronal population makes it possible to examine the role of these AChergic neurons and their cortical innervation in the processes of learning and memory. This chapter thus conducts a variety of behavioral tests and observations in order to assess the cognitive capabilities in the rat and measured biochemical parameters, such as ChAT and AChE after inducing NBM lesions using electricity and neurotoxins. This chapter discusses recent evidence of whether the NBM AChergic system really plays a significant role in the learning and memory processes.
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