Archival ReportAnhedonia Following Early-Life Adversity Involves Aberrant Interaction of Reward and Anxiety Circuits and Is Reversed by Partial Silencing of Amygdala Corticotropin-Releasing Hormone Gene
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Animals
Primiparous, time-pregnant Sprague Dawley rat dams were obtained from Harlan (now Envigo, Livermore, CA) on embryonic day 15, and maintained in an uncrowded, quiet animal facility room on a 12-hour light/dark cycle with ad libitum access to lab chow and water. Parturition was checked daily, and the day of birth was considered postnatal day 0. Four separate cohorts of rats were used, as described below. All experiments were performed in accordance with National Institutes of Health guidelines
Preference for Sucrose Is Diminished in Adolescent Male Rats That Experienced Early-Life Adversity
Sucrose consumption was significantly lower in 56-day-old rats that had experienced early-life stress (F1,21 = 8.85, p < .01) (Figure 1B, C), in line with our prior report (15). This was the case for both absolute sucrose consumption as well as the proportion (%) of the dilute sucrose solution of overall fluid intake (Supplemental Figure S2A, B). Reduced sucrose preference is generally considered an indicator of anhedonia.
Aberrant Structural Connectivity of Stress and Pleasure/Reward Circuits in CES Rats
Complex behaviors including pleasure/reward and fear/anxiety are mediated
Discussion
Here we demonstrate that early-life adversity provokes severe anhedonia by altering interactions of pleasure/reward and stress-related networks involving CRF-producing neurons in the amygdala. Specifically, we found that CES caused anhedonia, measured as decreased sucrose preference and reduced social play. During the normally pleasurable experience of play, early-life stress resulted in augmented, abnormal activation of CRF-producing neurons in the ACe of adolescent rats compared with control
Acknowledgments and Disclosures
This work was supported by National Institutes of Health Grant Nos. RO1s MH73136, NS28912, and P50 MH096889 (to TZB), and a George E. Hewitt Foundation for Medical Research postdoctoral fellowship (to JLB).
We thank Gissell A. Sanchez, Jennifer Daglian, and Pamela A. See for technical assistance.
The authors report no biomedical financial interests or potential conflicts of interest.
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