DESCRIPTION:

335 differentially expressed in the nucleus accumbens of Long-Evans female rats reared in limited bedding and nesting (LBN) conditions. The effect of LBN on morphine self-administration was investigated. Bilateral NAc specimens were analyzed for gene expression using RNA-seq. Data available at GEO (accession number GSE160495). Data taken from Table S2. Data presented are p-adjusted values.

LABEL:

Female Rat DEGs NAc limited bedding and nesting

SCORE TYPE:

Q-Value

DATE ADDED:

2021-06-10

DATE UPDATED:

2022-05-24

SPECIES:

AUTHORS:

Evelyn Ordoñes Sanchez, Charlotte C Bavley, Andre U Deutschmann, Rachel Carpenter, Drew R Peterson, Reza Karbalaei, James Flowers, Charleanne M Rogers, Miranda G Langrehr, Cory S Ardekani, Sydney T Famularo, Angela R Bongiovanni, Melissa C Knouse, Stan B Floresco, Lisa A Briand, Mathieu E Wimmer, Debra A Bangasser

TITLE:

Early life adversity promotes resilience to opioid addiction-related phenotypes in male rats and sex-specific transcriptional changes.

JOURNAL:

Proceedings of the National Academy of Sciences of the United States of America Feb 2021, Vol 118, pp. None

ABSTRACT:

Experiencing some early life adversity can have an "inoculating" effect that promotes resilience in adulthood. However, the mechanisms underlying stress inoculation are unknown, and animal models are lacking. Here we used the limited bedding and nesting (LBN) model of adversity to evaluate stress inoculation of addiction-related phenotypes. In LBN, pups from postnatal days 2 to 9 and their dams were exposed to a low-resource environment. In adulthood, they were tested for addiction-like phenotypes and compared to rats raised in standard housing conditions. High levels of impulsivity are associated with substance abuse, but in males, LBN reduced impulsive choice compared to controls. LBN males also self-administered less morphine and had a lower breakpoint on a progressive ratio reinforcement schedule than controls. These effects of LBN on addiction-related behaviors were not found in females. Because the nucleus accumbens (NAc) mediates these behaviors, we tested whether LBN altered NAc physiology in drug-naïve and morphine-exposed rats. LBN reduced the frequency of spontaneous excitatory postsynaptic currents in males, but a similar effect was not observed in females. Only in males did LBN prevent a morphine-induced increase in the AMPA/NMDA ratio. RNA sequencing was performed to delineate the molecular signature in the NAc associated with LBN-derived phenotypes. LBN produced sex-specific changes in transcription, including in genes related to glutamate transmission. Collectively, these studies reveal that LBN causes a male-specific stress inoculation effect against addiction-related phenotypes. Identifying factors that promote resilience to addiction may reveal novel treatment options for patients. PUBMED: 33593913
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