Dopamine cell firing can encode errors in reward prediction, providing a learning signal to guide future behavior. Yet dopamine is also a key modulator of motivation, invigorating current behavior. Existing theories propose that fast (“phasic”) dopamine fluctuations support learning, while much slower (“tonic”) dopamine changes are involved in motivation. We examined dopamine release in the nucleus accumbens across multiple time scales, using complementary microdialysis and voltammetric methods during adaptive decision-making. We first show that minute-by-minute dopamine levels covary with reward rate and motivational vigor. We then show that second-by-second dopamine release encodes an estimate of temporally-discounted future reward (a value function). We demonstrate that changing dopamine immediately alters willingness to work, and reinforces preceding action choices by encoding temporal-difference reward prediction errors. Our results indicate that dopamine conveys a single, rapidly-evolving decision variable, the available reward for investment of effort, that is employed for both learning and motivational functions.

The involvement of dopamine within the nucleus accumbens in the formation and maintenance of pair bonds was assessed in a series of experiments using the monogamous prairie vole. We show that dopamine transmission that promotes pair bond formation occurs within the rostral shell of the nucleus accumbens, but not in its core or caudal shell. Within this specific brain region, D1- and D2-like receptor activation produced opposite effects: D1-like activation prevented pair bond formation, whereas D2-like activation facilitated it. After extended cohabitation with a female, male voles showed behavior indicative of pair bond maintenance-namely, selective aggression towards unfamiliar females. These voles also showed a significant upregulation in nucleus accumbens D1-like receptors, and blockade of these receptors abolished selective aggression. Thus, neuroplastic reorganization of the nucleus accumbens dopamine system is responsible for the enduring nature of monogamous pair bonding. Finally, we show that this system may also contribute to species-specific social organization.

Transient surges of dopamine in the nucleus accumbens are associated with drug seeking. Using a voltammetric sensor with high temporal and spatial resolution, we demonstrate differences in the temporal profile of dopamine concentration transients caused by acute doses of nicotine, ethanol, and cocaine in the nucleus accumbens shell of freely moving rats. Despite differential release dynamics, all drug effects are uniformly inhibited by administration of rimonabant, a cannabinoid receptor (CB 1 ) antagonist, suggesting that an increase in endocannabinoid tone facilitates the effects of commonly abused drugs on subsecond dopamine release. These time-resolved chemical measurements provide unique insight into the neurobiological effectiveness of rimonabant in treating addictive disorders.

Although the role of nucleus accumbens (NAcc) dopamine (DA) in reward learning has been extensively studied, few investigations have addressed its involvement in learning socially relevant information. Here, we have examined the involvement of NAcc DA in social attachment of the "monogamous" prairie vole (Microtus orchrogaster). We first demonstrated that DA is necessary for the formation of social attachment in male prairie voles, because administration of haloperidol blocked, whereas apomorphine induced, partner-preference formation. We then provided the first descriptions of DA neuroanatomy and tissue content in vole NAcc, and mating appeared to induce a 33% increase in DA turnover. We also showed that administration of haloperidol directly into the NAcc blocked partner preferences induced by mating and apomorphine. In addition, administration of apomorphine into the NAcc but not the caudate putamen induced partner preferences in the absence of mating. Together, our data support the hypothesis that NAcc DA is critical for pair-bond formation in male prairie voles.

Preferential enhancement of dopamine transmission within the nucleus accumbens (NAc) shell is a fundamental aspect of the neural regulation of cocaine reward. Despite its importance, the nature of this effect is poorly understood. Here, we used fast-scan cyclic voltammetry to examine specific transmission processes underlying cocaine-evoked increases in dopamine transmission within the NAc core and shell. Initially, we examined altered terminal dopamine concentrations following global autoreceptor blockade. This was the first examination of autoreceptor regulation of naturally occurring phasic dopamine transmission and provided a novel characterization of specific components of dopamine neurotransmission. Comparison of increased dopamine signaling evoked by autoreceptor blockade and cocaine administration allowed robust resolution between increased frequency, concentration, and duration of phasic dopamine release events following cocaine delivery. Cocaine increased dopamine transmission by slowed uptake and increased concentration of dopamine released in the core and shell. However, an additional increase in the number phasic release events occurred only within the NAc shell and this increase was eliminated by inactivation of midbrain dopaminergic neurons. This represents the first evidence that cocaine directly increases the frequency of dopamine release events and reveals that this is responsible for preferentially increased dopamine transmission within the NAc shell following cocaine administration. Additionally, cocaine administration resulted in a synergistic increase in dopamine concentration and sub-region differences were abolished when cocaine was administered in the absence of autoregulation.Together, these results demonstrate that cocaine administration results in a temporally and regionally specific increase in phasic dopamine release that is significantly regulated by dopamine autoreceptors. The reinforcing properties of cocaine are significantly mediated by enhanced dopamine transmission (Kelley, 2004;Wise, 2004;Everitt and Robbins, 2005) and cocaine exerts its greatest increase in extracellular dopamine concentration ([DA]) within the shell sub-region of the nucleus accumbens (NAc) (Di Chiara and Bassareo, 2007). Cocaine increases [DA] by slowing uptake via blockade of dopamine transporters (DAT) (Giros et al., 1996) and by increasing the amount of dopamine exocytosed through mobilization of vesicles normally unavailable for release (Venton et al., 2006). However, neither mechanism can account for preferential enhancement of dopamine transmission within the NAc shell, because both are mediated through terminal DATs and DAT expression is significantly lower in the NAc shell compared to the core (Nirenberg et al., 1997). KeywordsIt has been suggested that this paradox may be explained by an increased number of dopamine release events within the shell following cocaine administration (Di Chiara and Bassareo, 2007). However, this hypothesis cannot be confirmed using microdialysis because it m...