Nicotine-dopamine-transporter interactions during reward-based decision making

Eur Neuropsychopharmacol. 2016 Jun;26(6):938-47. doi: 10.1016/j.euroneuro.2016.03.011. Epub 2016 Apr 22.

Abstract

Our everyday-life comprises a multitude of decisions that we take whilst trying to maximize advantageous outcomes, limit risks and update current needs. The cognitive processes that guide decision making as well as the brain circuits they are based on are only poorly understood. Numerous studies point to a potential role of dopamine and nicotine in decision making but less is known about their interactions. Here, 26 healthy male subjects performed the Iowa Gambling Task (IGT) in two sessions following the administration of either nicotine or placebo. Striatal dopamine transporter (DAT) binding was measured by single-photon emission computed tomography (SPECT). Results indicate that lower DAT levels were associated with better performance in the IGT (p=0.0004). Cognitive modelling analysis using the prospect valence learning (PVL) model indicated that low DAT subjects' performance deteriorated following nicotine administration as indicated by an increased learning rate and a decreased response consistency. Our results shed light on the neurochemistry underlying reward-based decision making in humans by demonstrating a significant interaction between nicotine and the DAT. The observed interaction is consistent with the hypothesized associations between DAT expression and extracellular dopamine levels, suggestive of an inverted U-shape relationship between baseline dopamine and magnitude in response to a pro-dopaminergic compound. Our findings are of particular interest in the context of psychiatric disorders where aberrant decision making represents a part of the core symptomatology, such as addiction, schizophrenia or depression.

Keywords: Cognitive modeling; Computational psychiatry; Iowa Gambling Task; Prospect valence learning; SPECT; Striatum.

MeSH terms

  • Adult
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism
  • Decision Making / drug effects*
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Extracellular Space / metabolism
  • Gambling / diagnostic imaging
  • Gambling / genetics*
  • Gambling / psychology*
  • Humans
  • Male
  • Nicotine / administration & dosage
  • Nicotine / pharmacology*
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / pharmacology*
  • Psychomotor Performance / drug effects
  • Reward*
  • Risk-Taking
  • Synaptic Transmission / drug effects
  • Tobacco Use Cessation Devices
  • Tomography, Emission-Computed, Single-Photon
  • Young Adult

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Nicotinic Agonists
  • Nicotine
  • Dopamine