assessing the effects of opioids on pathological memory by a computational model

Introduction: opioids hijack learning and memory formation mechanisms of brain and induce a pathological memory in the hippocampus. this effect is mainly mediated by modifications in glutamatergic system. speaking more precisely, opioids presence in a synapse inhibits blockage of n-methyl-d-aspartate receptor (nmdar) by mg^2+ , enhances conductance of nmdar and thus, induces false long-term potentiation (ltp). methods: based on experimental observations of different researchers, we developed a mathematical model for a pyramidal neuron of the hippocampus to study this false ltp. the model contains a spine of the pyramidal neuron with nmdar, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (ampars), and voltage-gated calcium channels (vgccs). the model also describes calmodulin-dependent protein kinase ii (camkii) and ampar phosphorylation processes which are assumed to be the indicators of ltp induction in the synapse. results: simulation results indicate that the effect of inhibition of blockage of nmdars by mg^2+ on the false ltp is not as crucial as the effect of nmdar’s conductance modification by opioids. we also observed that activation of vgccs has a dominant role in inducing pathological ltp. conclusion: our results confirm that preventing this pathological ltp is possible by three different mechanisms: 1. by decreasing nmdar’s conductance; and 2. by attenuating vgcc’s mediated current; and 3. by enhancing glutamate clearance rate from the synapse.