Maternal deprivation increases vulnerability to morphine dependence and disturbs the enkephalinergic system in adulthood
Open accessAbstract
Maternal deprivation can trigger long-lasting molecular and cellular modifications in brain functions and might facilitate the appearance of pathogenic behaviors. This study focuses on the vulnerability to develop morphine dependence in adult rats that were separated from their mother and littermates for 3 h per day for 14 d after birth and examines the adaptive changes in the enkephalinergic pathways. Place-preference conditioning was observed with 2 mg/kg morphine in deprived rats, whereas 5 mg/kg morphine was necessary to induce conditioning in nondeprived animals. A prolonged morphine conditioning was shown in deprived rats. A strong increase in oral morphine self-administration behavior and preference was observed in deprived rats. Only a very slight increase in preference for sucrose solution, a more ethological reinforcer known to interact with the opioid system, was shown in deprived rats. These results indicate that this postnatal environment change leads to a hypersensitivity to the reinforcing properties of morphine and to the development of morphine dependence. A significant decrease in preproenkephalin mRNA expression was observed in the nucleus accumbens and the caudate-putamen nucleus of deprived rats. The basal extracellular levels of the Met-enkephalin-like immunoreactivity in the nucleus accumbens were significantly lower in deprived rats when compared with nondeprived animals, whereas no change in mu-opioid receptor binding occurred. These results strongly support that maternal deprivation leads to a basal hypoactivity of the enkephalinergic system and hypersensitivity to morphine effects. Together, our results suggest that maternal deprivation in pups likely represents a risk factor for morphine dependence in adult rats.
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Maternal separation is associated with changes to the opioid system, but results conflict depending on methodology, showing both increases and decreases in endogenous peptide levels and ligand sensitivity.
“Changes to the opioid system are also apparent with maternal separation, but conflicting results also exist based on specific methodology, demonstrating both increases and decreases in levels of endogenous peptides (Ploj et al., 2003; Vazquez et al., 2005) as well as sensitivity to ligands (Kalinichev et al., 2001; Vazquez et al., 2005).”
From The effects of early life stress on reward processing (2018) · cites this paper as Vazquez et al., 2005
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References 53 · Cited by 101
- Authors
- Vazquez, V., Penit-Soria, J., Durand, C., Besson, M. J., Giros, B., & Daugé, V.
- Affiliations
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Besson, Marie Jo
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-05-04
- Volume
- 25
- Issue
- 18
- Pages
- 4453-4462
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6725024
- OpenAlex
- W2084169314
- Cited by
- 101
- References
- 53
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 12 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 2 · 2016: 5 · 2015: 2 · 2014: 3 · 2013: 9 · 2012: 3
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- maternal deprivation, morphine dependence, enkephalinergic system, opioid sensitivity, nucleus accumbens, caudate-putamen, preproenkephalin mRNA, met-enkephalin, mu-opioid receptor, morphine self-administration, place preference, sucrose preference
- MeSH terms
- Analysis of Variance, Animals, Animals, Newborn, Autoradiography, Behavior, Animal, Brain, Choice Behavior, Conditioning, Psychological, Dialysis, Dose-Response Relationship, Drug, Drinking Behavior, Enkephalin, Methionine, Enkephalins, Female, Maternal Deprivation, Morphine, Morphine Dependence, Narcotics, Nucleus Accumbens, Pregnancy, Protein Precursors, Radioimmunoassay, RNA, Messenger, Self Administration, Sucrose, Time Factors, Tritium, In Situ Hybridization, Receptors, Opioid, mu, Rats, Long-Evans, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, Rats
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