Document Detail


Multigenerational effects of adolescent morphine exposure on dopamine D2 receptor function.
MedLine Citation:
PMID:  23314440     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: 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.
OBJECTIVES: 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:
John J Byrnes; Nicole L Johnson; Lindsay M Carini; Elizabeth M Byrnes
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-13
Journal Detail:
Title:  Psychopharmacology     Volume:  227     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-26     Completed Date:  2013-10-28     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  263-72     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Analgesics, Opioid / administration & dosage,  pharmacology*
Animals
Behavior, Animal / drug effects*
Dopamine Agonists / administration & dosage,  pharmacology
Epigenesis, Genetic
Female
Gene Expression Regulation / drug effects
Male
Morphine / administration & dosage,  pharmacology*
Motor Activity / drug effects
Nucleus Accumbens / drug effects,  metabolism
Quinpirole / administration & dosage,  pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Dopamine D2 / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
R01 DA025674/DA/NIDA NIH HHS; R01DA25674/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Analgesics, Opioid; 0/Dopamine Agonists; 0/Receptors, Dopamine D2; 20OP60125T/Quinpirole; 76I7G6D29C/Morphine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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