Impaired cocaine-induced behavioral plasticity in the male offspring of cocaine-experienced sires.
behavioral sensitization
cocaine self-administration
epigenetics
multigenerational
transgenerational
Journal
The European journal of neuroscience
ISSN: 1460-9568
Titre abrégé: Eur J Neurosci
Pays: France
ID NLM: 8918110
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
16
05
2018
revised:
19
10
2018
accepted:
23
11
2018
pubmed:
20
12
2018
medline:
15
7
2020
entrez:
20
12
2018
Statut:
ppublish
Résumé
Our previous work indicated that male, but not female, offspring of cocaine-experienced sires display blunted cocaine self-administration. We extended this line of investigation to examine behavioral sensitization, a commonly used model of cocaine-induced behavioral and neuronal plasticity. Results indicated that male, but not female, offspring of cocaine-taking sires showed deficits in the ability of repeated systemic cocaine injections to induce augmented locomotor activity. The reduced cocaine sensitization phenotype in male progeny was associated with changes in histone post-translational modifications, epigenetic processes that regulate gene expression by controlling the accessibility of genes to transcriptional machinery, in the nucleus accumbens of first-generation male progeny. Thus, five histone post-translational modifications were significantly altered in the male progeny of cocaine-exposed sires. In contrast, self-administration of nicotine was unaltered in male and female offspring suggesting that the intergenerational effects of paternal cocaine taking may be drug-specific. Interestingly, the reduced sensitivity to cocaine previously observed in the male offspring of cocaine-taking sires dissipated in the grand-offspring. Both male and female grand-progeny of cocaine-exposed sires showed unaltered cocaine-induced behavioral sensitization and cocaine self-administration. Taken together, these findings indicate that paternal cocaine taking produces changes in multiple cocaine addiction-related behaviors in male progeny, which do not persist beyond the first generation of offspring. Moreover, the altered sensitivity to cocaine in first-generation male progeny of cocaine-sired male offspring was associated with epigenetic modifications in the nucleus accumbens, a nucleus that plays a critical role in cocaine-associated behavioral plasticity.
Identifiants
pubmed: 30565761
doi: 10.1111/ejn.14310
pmc: PMC6559866
mid: NIHMS1002750
doi:
Substances chimiques
Dopamine Uptake Inhibitors
0
Cocaine
I5Y540LHVR
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1115-1126Subventions
Organisme : NIDA NIH HHS
ID : R01037897
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA037897
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA039393
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : AI118891
Pays : International
Organisme : NIDA NIH HHS
ID : K02 DA018678
Pays : United States
Organisme : NIDA NIH HHS
ID : T32 DA028874
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA040837
Pays : United States
Organisme : NIDA NIH HHS
ID : K02 DA18678
Pays : United States
Organisme : NIDA NIH HHS
ID : K01 DA039308
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA033641
Pays : United States
Organisme : NIGMS NIH HHS
ID : GM110104
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI118891
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM110174
Pays : United States
Informations de copyright
© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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