title: Viral over-expression of D1 dopamine receptors in the prefrontal cortex increase high-risk behaviors in adults: comparison with adolescents.
abstract: BACKGROUND
  Adolescents are often described as "lacking brakes" resulting in an increase in several behaviors associated with risk for addiction. Prefrontal cortex dopamine and cortico-limbic interaction play an important role in addiction, and we have previously shown that the dopamine D1 receptor is elevated on prelimbic prefrontal output neurons in adolescent rats. We hypothesized that a constellation of risk-related behaviors is mediated by prefrontal output neuron expression of D1.
  
  
  OBJECTIVE
  We aimed to determine the role of the dopamine D1 receptor in behavioral and neural correlates of risk for addiction that are often observed in adolescents. Therefore, high-risk behaviors as well as subcortical D2 receptor expression were investigated in adult animals with experimentally elevated D1 on prefrontal glutamatergic neurons.
  
  
  METHODS
  A lentiviral vector that selectively expressed the D1 receptor within glutamate neurons was injected in the prelimbic prefrontal cortex of adult male rats. Place conditioning to cocaine, alcohol, and nicotine, as well as delay discounting, novelty preferences, anxiety, cocaine self-administration, and sucrose preferences were assessed.
  
  
  RESULTS
  Virally mediated D1 over-expression in adults leads to stronger drug-cue associations and greater consumption of sweet solutions, elevates bias towards immediate satisfaction rather than delaying gratification, decreases anxiety, and causes rats to work harder for and take more cocaine. Furthermore, elevated cortical D1 reduces D2 receptors in the accumbens (a putative risk marker).
  
  
  CONCLUSIONS
  Together, these data suggest a common mechanism for increased motivational drive to seek and consume substances with hedonic value, consistent with adolescent addictive processes.
authors.affiliation: Department of Psychiatry, McLean Hospital, Harvard Medical School, 115 Mill St., Belmont, MA, 02478, USA.
authors.forename: Kai C
authors.initials: KC
authors.lastname: Sonntag
authors.forename: Heather C
authors.initials: HC
authors.lastname: Brenhouse
authors.forename: Nadja
authors.initials: N
authors.lastname: Freund
authors.forename: Britta S
authors.initials: BS
authors.lastname: Thompson
authors.forename: Matthew
authors.initials: M
authors.lastname: Puhl
authors.forename: Susan L
authors.initials: SL
authors.lastname: Andersen
mesh_terms: D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D065786:Delay Discounting / Q000502:physiology; D019422:Dietary Sucrose / Q000008:administration & dosage; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005247:Feeding Behavior / Q000502:physiology; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics; D008297:Male; D009042:Motivation / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000254:growth & development / Q000502:physiology; D017397:Prefrontal Cortex / Q000254:growth & development* / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012309:Risk-Taking; D013028:Space Perception / Q000187:drug effects / Q000502:physiology
chemical_list: D002492:Central Nervous System Depressants; D019422:Dietary Sucrose; D018765:Dopamine Uptake Inhibitors; D018722:Nicotinic Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000431:Ethanol; D009538:Nicotine; D003042:Cocaine