SIGMA 1 RECEPTOR SELECTIVE LIGAND ATTENUATES SCOPOLAMINE INDUCED IMPAIRMENT IN LEARNING AND MEMORY

Purpose: Cognitive deficit is seen in patients with Alzheimer's disease, Parkinson's disease, after brain traumatic injury and stroke. Cognitive deficit is mainly due to the alteration in the cholinergic pathway. All currently prescribed therapeutic drugs provide only symptomatic relief and become ineffective as the disease progresses. Therefore, additional novel therapeutic agents need to be developed to slow or stop the progressive loss of memory forming cells. In this project, we will focus on characterizing a ligand selective at sigma 1 receptor for neuroprotection. Methods: A filtration-binding assay was used to characterize the binding properties of novel sigma compound at D2 like dopamine receptors and at sigma receptors. C57BL/6J mice injected with scopolamine were used as our experimental model to evaluate the cognitive properties of test drug. The neuroprotective properties were evaluated using water maze, active avoidance test and novel objet recognition tests. Results: Scopolamine treated animals exhibited impaired learning and memory in water maze and active avoidance test. Animals pre-treated with test drug attenuated the scopolamine-mediated effect. Conclusions: Test drug was able to attenuate the scopolamine-induced impairment in learning and memory.