Diurnal Variation in Motivation, Cocaine Value, and In Vivo Dopamine Release

• Published in: The FASEB journal 2022-05, Vol.36 (S1), p.n/a
• Main Authors: Iacino, Melody C‐L, Stowe, Taylor A., Pitts, Elizabeth G., Ferris, Mark J.
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2022.36.S1.R3786

Circadian rhythms have been shown to influence a number of psychiatric disorders, like substance use disorder (SUD). For example, individuals with evening chronotypes (i.e. night owls) express higher vulnerability to drug‐craving and drug‐taking behaviors. Similarly, the mesolimbic dopamine (DA) system, which is an essential circuit in these behaviors, exhibits diurnal rhythms in activity and function. Although diurnal rhythms have been documented in both drug‐taking and DA dynamics, it remains unclear whether these variations in DA confer with variations in‐drug taking. Here, we utilized in vivo fast scan cyclic voltammetry and a behavioral economic analysis of cocaine self‐administration to examine time‐of‐day variations in in vivo DA release, motivation, and cocaine value. We hypothesize that the degree to which the magnitude of mesolimbic DA release in the nucleus accumbens (NAc) varies across time will correspond diurnal variations found in motivation to take cocaine. We found that in vivo DA release was increased across the dark cycle in comparison to time‐points in the light cycle. We found no difference in cocaine intake in rats across time‐of‐day when cocaine “cost” was low and easy to obtain (Q0). However, we found that rats in the mid‐point of their dark cycles were more persistent in maintaining high cocaine intake as the “cost” or effort to maintain blood‐levels increased within their session in comparison to rats midway through their light cycle. These novel data suggest that specific time‐points across the dark cycle are associated with corresponding increases in DA and motivation to self‐administer cocaine under high, but no low, cost conditions. Understanding this dynamic modulation of diurnal variations may provide another therapeutic avenue for the circadian intervention of SUDs as well as target time‐points at which current pharmacotherapies might be most effective.