en Computational Neuroscience Computational Neuroscience Original Original <p dir="LTR" style="text-align: justify;"><strong>Introduction:</strong> 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 Mg2+ , enhances conductance of NMDAR and thus, induces false Long-Term Potentiation (LTP).&nbsp;<br> <strong>Methods: </strong>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, &alpha;-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.&nbsp;<br> <strong>Results:</strong> Simulation results indicate that the effect of inhibition of blockage of NMDARs by Mg2+ on the false LTP is not as crucial as the effect of NMDAR&rsquo;s conductance modification by opioids. We also observed that activation of VGCCs has a dominant role in inducing pathological LTP.&nbsp;<br> <strong>Conclusion:</strong> Our results confirm that preventing this pathological LTP is possible by three different mechanisms: 1. By decreasing NMDAR&rsquo;s conductance; and 2. By attenuating VGCC&rsquo;s mediated current; and 3. By enhancing glutamate clearance rate from the synapse.&nbsp;</p> Opioids, Memory of addiction, Synaptic plasticity, Long-Term Potentiation (LTP), Hippocampus 275 288 http://bcn.iums.ac.ir/browse.php?a_code=A-10-1150-1&slc_lang=en&sid=1 Mehdi Borjkhani m.borjkhani@ut.ac.ir 13700319475328460016376 13700319475328460016376 No Motor Control and Computational Neuroscience Laboratory, School of Electrical & Computer Engineering, College of Engineering, University of Tehran, Tehran, Iran. Fariba Bahrami fbahrami@ut.ac.ir 13700319475328460016377 13700319475328460016377 Yes Motor Control and Computational Neuroscience Laboratory, School of Electrical & Computer Engineering, College of Engineering, University of Tehran, Tehran, Iran. Mahyar Janahmadi mjanahmadi@yahoo.com 13700319475328460016378 13700319475328460016378 No Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.