Role of serotonin transporter function in rat orbitofrontal cortex in impulsive choice

Mahesh Darna, Jonathan J. Chow, Justin R. Yates, Richard J. Charnigo, Joshua S. Beckmann, Michael T. Bardo, Linda P. Dwoskin

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Impulsivity is a multi-faceted personality construct that plays a prominent role in drug abuse vulnerability. Dysregulation of 5-hydroxytryptamine (serotonin, 5-HT) systems in subregions of the prefrontal cortex has been implicated in impulsivity. Extracellular 5-HT concentrations are regulated by 5-HT transporters (SERTs), indicating that these transporters may be important molecular targets underlying individual differences in impulsivity and drug abuse vulnerability. The present study evaluated the role of SERT in mediating individual differences in impulsivity. Rats were tested for both impulsive action using the cued go/no-go task and for impulsive choice using a delay discounting task in a counterbalanced design. Following behavioral evaluation, Km and Vmax were obtained from kinetic analysis of [3H]5-HT uptake by SERT using synaptosomes prepared from both orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) obtained from each individual rat. Vmax for SERT in OFC, but not mPFC, was negatively correlated with mean adjusted delay scores in the delay discounting task. In contrast, Vmax for SERT in OFC and mPFC was not correlated with performance in the cued go/no-go task. To further evaluate the relationship between SERT function and impulsive choice, a selective SERT inhibitor, fluoxetine (0, 15, 50 and 150pmol/side) was microinjected bilaterally into OFC and effects on the delay discounting task determined. Following stabilization of behavior, fluoxetine increased mean adjusted delay scores (decreased impulsivity) in high impulsive rats compared to saline microinjection, but had no effect in low impulsive rats. These ex vivo and in vivo results suggest that enhanced SERT function in OFC underlies high impulsive choice behavior.

Original languageEnglish
Pages (from-to)134-142
Number of pages9
JournalBehavioural Brain Research
Volume293
DOIs
StatePublished - Oct 5 2015

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grant P50 DA05312 (Center for Drug Abuse Research Translation) and UL1 TR000117. The authors declare no conflict of interest.

Publisher Copyright:
© 2015 Elsevier B.V..

Keywords

  • Cued go/no-go
  • Delay discounting
  • Impulsivity
  • Serotonin transporter

ASJC Scopus subject areas

  • Behavioral Neuroscience

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