Interactive role of acid sensing ion channels and glutamatergic system in opioid dependence

Dysregulation in glutamatergic receptors and transporters has been found to mediate drugs of abuse, including morphine. Among glutamate receptors, ionotropic glutamate receptors (iGluRs) are altered with exposure to drugs of abuse. Acid-sensing ion channels (ASICs) are ligand (H+)-gated channels, which are expressed at the excitatory synaptic clefts and play a role in drug dependence. Overexpression of a specific ASIC subtype, ASIC1a, attenuated reinstatement of cocaine. ASICs are revealed to be involved in cocaine and morphine seeking behaviors, and these effects are mediated through modulation of glutamatergic receptors. In this review, we discussed the interactive role of ASICs and glutamate receptors, mainly iGluRs, in opioid dependence. ASICs are also expressed in astrocytes and are suggested to be involved on regulating glutamate uptake. However, little is known about the coupling between ASICs and the astroglial glutamate transporters. In addition, this review discussed the role of nitric oxide in the modulation of ASIC function and potentially opioid dependence. We also discussed the role of ASICs in the modulation of the function of both glutamatergic receptors in post-synaptic neurons and glutamatergic transporters in astrocytes in animals exposed to drugs of abuse.