A mathematical model for neuron astrocytes interactions in hippocampus during addiction

Abstract

Addiction is a chronic disorder whereby addicted individuals compulsively engage in drug seeking despite its negative consequences. Hippocampus has unavoidable role in addiction because of its importance in learning and memory. Any modification of hippocampal cells alters dopamine levels in NAc and firing rates of VTA dopaminergic cells. In order to have a better understanding of the addiction in cellular level, we present a mathematical model of a tripartite synapse in hippocampus. The proposed model can show some functions of synapses under addiction that may contribute to drug seeking and relapse behaviors. The model is based on glutamate alterations in synaptic cleft during drug abuse. Experimental studies suggest that during drug abuse, NMD AR dependent synaptic transmission is increased. According to our simulation results, dysfunction of astrocyte has a significant role in initiating addiction. Since healthy astrocytes has a comprehensive control over synaptic interactions it may use to treat addicted related behaviors. Also, we may conclude that addiction causes abnormalities on postsynaptic signaling such as NMDA currents. Furthermore, we may suggest that drug induced D-serine enhancement in synaptic cleft potentiate post synaptic calcium influx and LTP.