Opioid-induced structural and functional plasticity of medium-spiny neurons in the nucleus accumbens

Abstract

Opioid Use Disorder (OUD) is a chronic relapsing clinical condition with tremendous morbidity and mortality that frequently persists, despite treatment, due to an individual's underlying psychological, neurobiological, and genetic vulnerabilities. Evidence suggests that these vulnerabilities may have neurochemical, cellular, and molecular bases. Key neuroplastic events within the mesocorticolimbic system that emerge through chronic exposure to opioids may have a determinative influence on behavioral symptoms associated with OUD. In particular, structural and functional alterations in the dendritic spines of medium spiny neurons (MSNs) within the nucleus accumbens (NAc) and its dopaminergic projections from the ventral tegmental area (VTA) are believed to facilitate these behavioral sequelae. Additionally, glutamatergic neurons from the prefrontal cortex, the basolateral amygdala, the hippocampus, and the thalamus project to these same MSNs, providing an enriched target for synaptic plasticity. Here, we review literature related to neuroadaptations in NAc MSNs from dopaminergic and glutamatergic pathways in OUD. We also describe new findings related to transcriptional, epigenetic, and molecular mechanisms in MSN plasticity in the different stages of OUD.

Keywords: Addiction; Dendrites; Dendritic spines; Heroin; Medium-spiny neurons; Morphine; Nucleus accumbens; Opioid Use Disorder; Plasticity.

Figure 1.. Opioid-Induced Plasticity of the Nucleus Accumbens in Relation to Addiction Behavior and Corresponding Affective Experience.

A schematic depiction of the cycle of addiction in relation to both behavior and affective experience. This figure represents the combination and adaptation of a diagram from Koob and Le Moal (2001) and a diagram by Russell and Feldman Barrett (1999). The circumplex at the center of the figure represents the affective experiences that tend to correspond to the two discrete behavioral phases of addiction: acute involvement with a substance or activity and acute/protracted abstinence. These affective experiences tend to vary with respect to valence (horizontal axis) and intensity (vertical axis), depending on the substance or activity of involvement, the duration of involvement, and the duration of abstinence. The arrows constituting the outer circle represent the cyclical nature of the addictive experience, which coincides with both behavior and affective states. The individual affective states that are indicated within the circumplex are not meant to be exhaustive, but rather representative of the types of states that characterize a given quadrant (e.g., high intensity, negative valence). The paradigms indicated beneath the circumplex refer to the types of experimental designs that correspond to either the involvement or abstinence phase of the addiction cycle. Abbreviations: SA = Self-administration; Sensi = Sensitization; CPP = Conditioned Place Preference; CPA = Conditioned Place Aversion. Beneath these experimental paradigms are the structural plasticity changes that that have been found in the preponderance of studies within the nucleus accumbens.