Repeated exposure to addictive drugs leads to the increase in drug-seeking behavior (the effort to obtain a drug when it is unavailable) and behavioral sensitization (a neuroadaptive process in which repeated drug exposure leads to a progressively stronger and long-lasting behavioral response to a drug). Over the past two decades, extensive research has characterized the drug-induced plasticity that occurs within neural circuits that regulate motivation and reward in parallel with the behavioral changes that occur in animal models of addiction. These structural and functional adaptations are responsible for the persistent craving and reduced regulation of drug use that characterize addiction, as well as changes in the sensitivity to the effects of a drug.

A key hub of the reward system is the nucleus accumbens (NAc). Medium spiny neurons (MSNs) within the NAc display cell-specific adaptations after administration of the psychostimulant drug cocaine. These adaptations vary based on the neuronal inputs and outputs of the MSNs, location within the NAc, and dopamine D1- or D2-receptor expression (Zinsmaier et al., 2022). For example, a cocaine-induced strengthening of synapses between dorsomedial prefrontal afferents and NAc core MSNs promotes cocaine seeking (Zinsmaier et al., 2022). Understanding the mechanisms underlying this plasticity could contribute to the development of effective treatments for cocaine use disorder (CUD), and genes and signaling cascades that are involved may be potential therapeutic targets.

A network of actin filaments beneath the plasma membrane supports the shape of dendritic spines, and rearrangement of this meshwork, mediated by actin binding proteins, produces the structural changes necessary for strengthening or weakening synaptic connections. Actin polymerization is required for long-term potentiation and modulates the function of neurotransmitter receptors at the synapse. Moreover, actin filaments interact with signaling molecules that regulate synaptic plasticity (Pandey and …

Correspondence should be addressed to Margareth Nogueira at mdebritouab.edu.