Heterogeneous dopamine signals support distinct features of motivated actions: implications for learning and addiction

Abstract

Despite decades of research, investigations into effective neural and pharmacological therapies for many drugs of abuse, such as cocaine, have produced no FDA-approved approaches. This difficulty derives from the complexity of substance use disorders, which encompass a variety of behavioral, psychological, and neural circuit-based changes that occur as a result of repeated experience with the drug. Dopamine signaling has been demonstrated to play a key role in several aspects of drug abuse-from mediating its reinforcing properties and drug-seeking to triggering relapse-while also mediating a number of important aspects of normal (nondrug related) motivated behaviors and actions. Real-time recording methods such as in vivo voltammetry, electrophysiology, and calcium imaging demonstrate that the signaling properties of dopamine for motivationally relevant stimuli are highly dynamic and spatiotemporally circumscribed within afferent target regions. In this review, we identify the origins and functional consequences of heterogeneous dopamine release in the limbic system, and how these properties are persistently altered in the drug-experienced brain. We propose that these spatiotemporally parallel dopaminergic signals are simultaneously available to the animal, but that these circuits are impaired following prolonged drug experience by disrupting the location and content of dopamine signals in afferent target regions. These findings are discussed in the context of relapse and pathways to discovering new treatments for addiction disorders.

Prelimbic cortex neural encoding dynamically tracks expected outcome value

“…One possibility is that the NAc is more involved in experiential updating of actual outcome value. This would be consistent with the idea that the NAc core specifically is involved in learning (or re-learning) cue-outcome associations [37][38][39].…”

Voluntary alcohol consumption during distinct phases of adolescence differentially alters adult fear acquisition, extinction and renewal in male and female rats

“…Alternatively, these data may implicate alcohol-mediated changes in dopamine function and reflect recent findings that fear learning and discrimination can be accelerated by phasic increases in dopamine during conditioning. Mesolimbic projections from ventral tegmental area (VTA) to nucleus accumbens (Saddoris et al, 2018(Saddoris et al, , 2015, and/or mesoamygdalar projections from VTA to BLA could potentiate acquisition of aversive learning and enhance discrimination between different threats (Jo et al, 2018;Tang et al, 2020). Accordingly, accelerated fear acquisition in the Early-EtOH group could be linked to better learning in limbic regions, including BLA.…”