Investigating the Mechanisms Involved in Scopolamine-induced Memory Degradation.

Abstract

In the present study, the mechanisms involved in scopolamine-induced memory impairment have been investigated. The molecular events that take place during memory mostly include mechanisms that are seen in the acquisition phase. Results showed that one of the mechanisms of memory destruction caused by scopolamine, in addition to weakening the cholinergic system, is the indirect effect of scopolamine on other neurotransmitter systems, including the glutamatergic system. Scopolamine injection increases dopamine by inhibiting M2/4 muscarinic autoreceptors. These autoreceptors are located on dopaminergic presynaptic neurons, and their activation reduces the release of dopamine. Therefore, blocking these autoreceptors by scopolamine can increase the release of dopamine. Both D1 and D2 receptors are involved in learning and memory processes. In general, stimulation of dopamine D1 receptors follows an inverted U-shaped dose-response curve, meaning that both insufficient and excessive amounts of dopamine cause memory impairment. Therefore, an indirect effect on the dopaminergic system can be one of the scopolamine-induced memory impairment mechanisms. Effects on cell membrane potential and neuron plasticity, and interaction with acetylcholine are among other mechanisms. Serotonin plays a complex role in memory and learning. Serotonin receptors (5-HT2A) also play a role in memory function by affecting calcium transport. This action is similar to dopamine and other G-protein-coupled receptors, which activate phospholipase C, enter calcium into the cell, and activate calcineurin. Activation of 5-HT2A and 5-HT4 receptors by specific agonists of these receptors enhances long-term potentiation (LTP), which plays a significant role in memory. On the other hand, specific 5-HT3 receptor antagonist improves LTP. The 5-HT6 receptor antagonist can improve memory function. Therefore, different serotonin receptors have different roles in memory function, and the interaction between scopolamine and these receptors needs further study. It has been shown that histamine increases the secretion of acetylcholine in the hippocampus, and postsynaptic H1 and presynaptic H3 receptors play a major role in memory and learning; however, whether scopolamine can cause memory impairment through interaction with histamine receptors has been not reviewed.