Early life adversity promotes resilience to opioid addiction-related phenotypes in male rats and sex-specific transcriptional changes
| Autor: | Debra A. Bangasser, Cory S. Ardekani, Mathieu E. Wimmer, Charlotte C. Bavley, Rachel Carpenter, Miranda G. Langrehr, Charleanne M. Rogers, Lisa A. Briand, Evelyn Ordoñes Sanchez, James Flowers, Angela R. Bongiovanni, Melissa C. Knouse, Reza Karbalaei, Andre U. Deutschmann, Drew R. Peterson, Sydney T. Famularo, Stan B. Floresco |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty media_common.quotation_subject AMPA receptor Nucleus accumbens Biology Impulsivity Receptors N-Methyl-D-Aspartate Nucleus Accumbens Sex Factors Internal medicine medicine Animals Rats Long-Evans Receptors AMPA media_common Multidisciplinary Behavior Animal Addiction Glutamate receptor Resilience Psychological Opioid-Related Disorders Phenotype Rats Endocrinology Animals Newborn Gene Expression Regulation Excitatory postsynaptic potential NMDA receptor Female medicine.symptom Transcriptome Stress Psychological |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 118(8) |
| ISSN: | 1091-6490 |
| Popis: | 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-naive 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|