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Multigenerational effects of adolescent morphine exposure on dopamine D2 receptor function
John J Byrnes1, Nicole L Johnson, Lindsay M Carini
1Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA. john.byrnes@tufts.edu
Psychopharmacology
|January 15, 2013
Summary
Adolescent opiate exposure in female rats altered their male offspring's (F1 and F2) response to dopamine receptor activation, suggesting potential long-term epigenetic impacts on motivated behaviors and psychopathology vulnerability.
Area of Science:
- Neuroscience
- Endocrinology
- Genetics
Background:
- Adolescent prescription opiate misuse is rising, particularly in females.
- Opioids significantly influence neuroendocrine function during critical developmental periods.
- Adolescent opiate exposure may have lasting consequences for females and their offspring.
Purpose of the Study:
- To model the transgenerational impact of adolescent opiate exposure in female rats.
- To investigate the effects of maternal adolescent morphine exposure on subsequent generations' neurobehavioral responses.
Main Methods:
- Female rats received morphine during adolescence.
- Locomotor sensitization to quinpirole (a dopamine D2/D3 agonist) was assessed in adult male progeny (F1 and F2).
- Females were drug-free for at least 3 weeks before conception to prevent direct fetal exposure.
Main Results:
- Progeny (F1 and F2) of morphine-exposed females showed reduced locomotor sensitization to quinpirole.
- Increased corticosterone secretion and upregulated kappa opioid receptor and dopamine D2 receptor (D2R) gene expression were observed in the nucleus accumbens.
- Behavioral and molecular changes occurred despite no direct fetal exposure to morphine.
Conclusions:
- Adolescent opiate exposure induces lasting modifications in D2R signaling in offspring.
- These modifications may increase offspring vulnerability to psychopathology, including addiction.
- Effects observed in F2 generation indicate potential transgenerational epigenetic modifications impacting motivated behavior systems.
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