Risky decision-making predicts dopamine release dynamics in nucleus accumbens shell

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 45; no. 2; pp. 266 - 275
• Main Authors: Freels, Timothy G., Gabriel, Daniel B. K., Lester, Deranda B., Simon, Nicholas W.
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.01.2020; Springer International Publishing
• Subjects: Amperometry; Animals; Decision making; Decision Making - physiology; Delay Discounting - physiology; Dopamine; Dopamine - metabolism; Dopamine receptors; Drug development; Footshock; Forebrain; Forecasting; Male; Medial forebrain bundle; Mental task performance; Nomifensine; Nucleus accumbens; Nucleus Accumbens - metabolism; Phenotypes; Psychopathology; Punishment; Rats; Rats, Long-Evans; Reinforcement; Risk-Taking; Therapeutic applications
• ISSN: 0893-133X; 1740-634X; 1740-634X
• DOI: 10.1038/s41386-019-0527-0

The risky decision-making task (RDT) measures risk-taking in a rat model by assessing preference between a small, safe reward and a large reward with increasing risk of punishment (mild foot shock). It is well-established that dopaminergic drugs modulate risk-taking; however, little is known about how differences in baseline phasic dopamine signaling drive individual differences in risk preference. Here, we used in vivo fixed potential amperometry in male Long-Evans rats to test if phasic nucleus accumbens shell (NACs) dopamine dynamics are associated with risk-taking. We observed a positive correlation between medial forebrain bundle-evoked dopamine release in the NACs and risky decision-making, suggesting that risk-taking is associated with elevated dopamine sensitivity. Moreover, "risk-taking" subjects were found to demonstrate greater phasic dopamine release than "risk-averse" subjects. Risky decision-making also predicted enhanced sensitivity to the dopamine reuptake inhibitor nomifensine, and elevated autoreceptor function. Importantly, this hyperdopaminergic phenotype was selective for risky decision-making, as delay discounting performance was not predictive of phasic dopamine release or dopamine supply. These data identify phasic NACs dopamine release as a possible therapeutic target for alleviating the excessive risk-taking observed across multiple forms of psychopathology.