Glial-neuronal ensembles: partners in drug addiction-associated synaptic plasticity

INTRODUCTION Drug addiction is manifested by a compulsive drive to take licit or illicit substances despite repeated severe adverse consequences (Volkow et al., 2012). Addiction is also accompanied by a vicious cycle of binges, abstinence, and relapses. Almost all drugs of abuse trigger euphoric feelings consequent to a rapid increase of dopamine levels in the mesolimbic system. Even after long periods of abstinence, addicts remain vulnerable to drug craving and/or relapses that can be triggered by stimuli previously associated with drugs (Koob and Volkow, 2010). These features of addiction suggest that drugs might cause a form of persistent neuroplasticity that is acutely responsive to environmental stimuli, with consequent compulsive drug-seeking and taking behaviors. Neural functions require the coordinated interactions of multiple neuronal cell types and a diverse population of glial cells. The three major glial cell types in the brain, astrocytes, oligodendrocytes, and microglia, communicate with each other and with neurons by using neurotransmitters, other small molecules, and gap junctions (Araque et al., 2014). Oligodendrocytes increase the speed of electrical transmission through nerve axons by forming the axonal myelin sheath and clustering ion channels at nodes of Ranvier (Nave, 2010). Microglia prune synapses in part by monitoring synaptic transmission (Schafer et al., 2013; Wake et al., 2013). Astrocytes can regulate synaptic transmission between neurons by modifying the concentration of extracellular potassium, controlling local blood flow, by releasing and/or taking up neurotransmitters or neuromodulators, by delivering nutrients to neurons, and by altering the geometry and volume of the brain extracellular space (Araque et al., 2014). This brief summary of glial functions suggests that these cells might play important roles in the long-term manifestations of substance use disorders, both in terms of addiction to these agents and their longterm neuropsychiatric consequences. In what follows, we discuss some recent findings that support the thesis that glial cells are part and parcel of the plastic mechanisms that are induced by drugs of abuse.