Accumbal μ-opioid receptors and salt taste-elicited hedonic responses in a rodent model of prenatal adversity, and their correlates using human functional genomics

Abstract

Prenatal adversity is associated with behavioral obesogenic features such as preference for palatable foods. Salt appetite may play a role in the development of adiposity and its consequences in individuals exposed to prenatal adversity, and sodium consumption involves individual differences in accumbal µ-opioid receptors function. We investigated the hedonic responses to salt and the levels of µ-opioid receptors and tyrosine hydroxylase in the nucleus accumbens (Nacc) of pups from an animal model of prenatal dietary restriction. In children, we evaluated the interaction between fetal growth and the genetic background associated with the accumbal µ-opioid receptor gene (OPRM1) expression on sodium consumption during a snack test. Sprague-Dawley dams were randomly allocated from pregnancy day 10 to receive an ad libitum (Adlib) or a 50% restricted (FR) diet. The pups’ hedonic responses to a salt solution (NaCl 2%) or water were evaluated on the first day of life. FR and Adlib pups differ in their hedonic responses to salt, and there were decreased levels of accumbal µ-opioid and p-µ-opioid receptors in FR pups. In humans, a test meal and genotyping from buccal epithelial cells were performed in 270 children (38 intrauterine growth restricted—IUGR) at 4 years old from a Canadian prospective cohort (MAVAN). The OPRM1 genetic score predicted the sodium intake in IUGR children, but not in controls. The identification of mechanisms involved in the brain response to prenatal adversity and its consequences in behavioral phenotypes and risk for chronic diseases later in life is important for preventive and therapeutic purposes.

Keywords:

• Prenatal adversity
• intrauterine growth restriction
• hedonic response
• salt appetite
• opioid system
• translational research

Acknowledgements

The authors acknowledge Zihan Wang and Sachin Patel for performing the genetic scores calculation.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by Canadian Institutes of Health Research (CIHR, PJT-166066, PI Silveira PP), and Natural Sciences and Engineering Research Council of Canada (NSERC, RGPIN-2018-05063, PI Silveira PP). Dr. Levitan acknowledges support from the Cameron Holcombe Wilson Chair in Depression studies, CAMH and University of Toronto.

Notes on contributors

Adrianne Rahde Bischoff

Adrianne Rahde Bischoff, MD, received her medical degree in Medicine from the Federal University of Rio Grande do Sul, Brazil. She completed a Neonatal Perinatal Medicine Fellowship at University of Toronto / Hospital for Sick Children, and a Neonatal Hemodynamics Fellowship at University of Iowa. Currently she is a Clinical Assistant Professor of Pediatrics-Neonatology at the University of Iowa, US.

Roberta Dalle Molle

Roberta Dalle Molle, PhD, received her Bachelor’s in Nutrition, and her MSc and PhD in Medicine (focus on Child and Adolescent Health) from the Federal University of Rio Grande do Sul, Brazil. This was followed by a postdoctoral fellowship at the McGill University. Currently she is a Research Associate at the Douglas Mental Health University Institute, Montreal, Canada.

Amanda Brondani Mucellini

Amanda Brondani Mucellini, PhD, received her Bachelor’s in Biology from the Federal University of Santa Maria, Brazil, and her MSc in Physiology and PhD in Psychiatry from the Federal University of Rio Grande do Sul, Brazil.

Irina Pokhvisneva

Irina Pokhvisneva, MSc, is a biostatistician at the Douglas Mental Health University Institute based in Montreal, Canada with expertise in data management, processing, and statistical analysis of longitudinal and cross-sectional studies. Her academic background lies in the fields of biostatistics and applied mathematics.

Robert D. Levitan

Robert D. Levitan, MD PhD, is a Full Professor in the Department of Psychiatry with a cross-appointment in the Department of Physiology, University of Toronto. Dr. Levitan holds the Cameron Parker Holcombe Wilson Chair in Depression studies at University of Toronto and CAMH. He is a full member of the Institute of Medical Sciences at University of Toronto.

Michael J. Meaney

Michael J. Meaney, PhD, is a James McGill Professor in the departments of Psychiatry and Neurology, and Neurosurgery at McGill University. He is also the Programme Director for the Translational Neuroscience domain at the Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR).

Patrícia P. Silveira

Patrícia P. Silveira, MD PhD, is an Associate Professor at the Department of Psychiatry at McGill University, Canada, with unique training that involves Neuroscience (PhD), Developmental Biology (postdoctoral training), Pediatrics and Neonatal Follow-up. She is also the Scientific Director of the Genomic & Epigenetics Pillar at the Ludmer Centre for Neuroinformatics and Mental Health.