Pre-clinical models of reward deficiency syndrome: A behavioral octopus

Neurosci Biobehav Rev. 2020 Aug:115:164-188. doi: 10.1016/j.neubiorev.2020.04.021. Epub 2020 Apr 28.


Individuals with mood disorders or with addiction, impulsivity and some personality disorders can share in common a dysfunction in how the brain perceives reward, where processing of natural endorphins or the response to exogenous dopamine stimulants is impaired. Reward Deficiency Syndrome (RDS) is a polygenic trait with implications that suggest cross-talk between different neurological systems that include the known reward pathway, neuroendocrine systems, and motivational systems. In this review we evaluate well-characterized animal models for their construct validity and as potential models for RDS. Animal models used to study substance use disorder, major depressive disorder (MDD), early life stress, immune dysregulation, attention deficit hyperactivity disorder (ADHD), post traumatic stress disorder (PTSD), compulsive gambling and compulsive eating disorders are discussed. These disorders recruit underlying reward deficiency mechanisms in multiple brain centers. Because of the widespread and remarkable array of associated/overlapping behavioral manifestations with a common root of hypodopaminergia, the basic endophenotype recognized as RDS is indeed likened to a behavioral octopus. We conclude this review with a look ahead on how these models can be used to investigate potential therapeutics that target the underlying common deficiency.

Keywords: APOSUS; Addiction; Alcohol use disorder; Alcohol-preferring P rat; Animal models of reward deficiency; Compulsive eating disorder; Dopamine; Early life stress; Gambling disorder; Helpless mouse (HL); Knockout rats; Maternal deprivation; PTSD; Reward; Roman; Wistar Kyoto (WKY) rat; mGluR2.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity*
  • Behavior, Addictive*
  • Depressive Disorder, Major*
  • Humans
  • Impulsive Behavior
  • Octopodiformes*
  • Reward