title: Multigenerational effects of adolescent morphine exposure on dopamine D2 receptor function.
abstract: BACKGROUND
  The use and misuse of prescription opiates in adolescent populations, and in particular, adolescent female populations, has increased dramatically in the past two decades. Given the significant role that opioids play in neuroendocrine function, exposure to opiates during this critical developmental period could have significant consequences for the female, as well as her offspring.
  
  
  OBJECTIVE
  In the current set of studies, we utilized the female rat to model the transgenerational impact of adolescent opiate exposure.
  
  
  METHODS
  We examined locomotor sensitization in response to the dopamine D2/D3 receptor agonist quinpirole in the adult male progeny (F1 and F2 generations) of females exposed to morphine during adolescence. All females were drug-free for at least 3 weeks prior to conception, eliminating the possibility of direct fetal exposure to morphine.
  
  
  RESULTS
  Both F1 and F2 progeny of morphine-exposed females demonstrated attenuated locomotor sensitization following repeated quinpirole administration. These behavioral effects were coupled with increased quinpirole-induced corticosterone secretion and upregulated kappa opioid receptor and dopamine D2 receptor (D2R) gene expression within the nucleus accumbens.
  
  
  CONCLUSIONS
  These results suggest significant modifications in response to repeated D2R activation in the progeny of females exposed to opiates during adolescence. Given the significant role that the D2R plays in psychopathology, adolescent opiate exposure could shift the vulnerability of future offspring to psychological disorders, including addiction. Moreover, that effects are also observed in the F2 generation suggests that adolescent opiate exposure can trigger transgenerational epigenetic modifications impacting systems critical for motivated behavior.
authors: Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA. john.byrnes@tufts.edu
authors: John J
authors: JJ
authors: Byrnes
authors: Nicole L
authors: NL
authors: Johnson
authors: Lindsay M
authors: LM
authors: Carini
authors: Elizabeth M
authors: EM
authors: Byrnes
mesh_terms: D000367:Age Factors; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D019257:Quinpirole / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D009020:Morphine