Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z

PLoS One. 2017 Apr 26;12(4):e0174774. doi: 10.1371/journal.pone.0174774. eCollection 2017.

Abstract

Dopaminergic reward dysfunction in addictive behaviors is well supported in the literature. There is evidence that alterations in synchronous neural activity between brain regions subserving reward and various cognitive functions may significantly contribute to substance-related disorders. This study presents the first evidence showing that a pro-dopaminergic nutraceutical (KB220Z) significantly enhances, above placebo, functional connectivity between reward and cognitive brain areas in the rat. These include the nucleus accumbens, anterior cingulate gyrus, anterior thalamic nuclei, hippocampus, prelimbic and infralimbic loci. Significant functional connectivity, increased brain connectivity volume recruitment (potentially neuroplasticity), and dopaminergic functionality were found across the brain reward circuitry. Increases in functional connectivity were specific to these regions and were not broadly distributed across the brain. While these initial findings have been observed in drug naïve rodents, this robust, yet selective response implies clinical relevance for addicted individuals at risk for relapse, who show reductions in functional connectivity after protracted withdrawal. Future studies will evaluate KB220Z in animal models of addiction.

MeSH terms

  • Animals
  • Brain / anatomy & histology
  • Brain / drug effects*
  • Brain / physiology
  • Brain Mapping
  • Catecholamines / pharmacology*
  • Cognition / drug effects
  • Dopamine Agents / pharmacology*
  • Hippocampus / anatomy & histology
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • Magnetic Resonance Imaging
  • Male
  • Monoamine Oxidase / pharmacology*
  • Neprilysin / pharmacology*
  • Nucleus Accumbens / anatomy & histology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiology
  • Placebo Effect
  • Rats
  • Rats, Long-Evans
  • Thalamic Nuclei / anatomy & histology
  • Thalamic Nuclei / drug effects
  • Thalamic Nuclei / physiology

Substances

  • Catecholamines
  • Dopamine Agents
  • KB220Z
  • Monoamine Oxidase
  • Neprilysin