Abstract
Rationale
Early environment can shape the development and function of the mesocorticolimbic dopamine (DA) system and represents a possible risk factor for adult pathologies. One critical variable in the early environment is nutrition, and exposure to high fat (HF) in adulthood is known to change this DA system.
Objectives
We tested whether perinatal HF intake in rats could have long-term effects on DA function and behavior in adult offspring.
Materials and methods
Rat dams were fed either a control (5% fat, CD) or high fat (30% fat, HF) diet during the last week of gestation and lactation, and adult offspring were tested (PND 56–90) after weaning on CD. Locomotor responses to acute and repeated doses of d-amphetamine (AMP, 0.75 mg/kg bw) were determined as were indices of DA function in the ventral tegmental area (VTA), nucleus accumbens (NAc), and the prefrontal cortex (PFC).
Results
Adult HF offspring displayed increased tyrosine hydroxylase expression in the VTA and NAc and significant increases in DA and DOPAC content in the NAc, suggesting an elevated DA tone in this target field. In the NAc, there were no significant changes in D1, D2 receptors, or DA transporter (DAT) levels between diet groups. Perinatal HF feeding reduced AMP-induced locomotion and behavioral sensitization to AMP, suggesting that early diet might have caused long-lasting desensitization of postsynaptic receptor mechanisms in the NAc.
Conclusions
Our results demonstrate that both synthetic activity in VTA neurons and the responsiveness of accumbens DA neurons is altered by maternal nutrition. These effects subside long after termination of exposure to the HF diet.
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Acknowledgements
We would like to thank Hong Long, Susan Xu, and Luc Moquin for their expert help with the animals, the autoradiography, and the use of the LC-EC system. This work was supported by a grant from the Canadian Institutes for Health Research (CIHR) grant #FRN 53350 to CDW and by a fellowship from the Fonds de Recherche en Santé du Quebec (FRSQ) to LN, and by a grant from the National Institute on Drug Abuse DA07610 to SMO.
Disclosure/Conflict of interest
All authors recognize having no potential or real conflict of interest related to the subject of the present report.
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Naef, L., Srivastava, L., Gratton, A. et al. Maternal high fat diet during the perinatal period alters mesocorticolimbic dopamine in the adult rat offspring: reduction in the behavioral responses to repeated amphetamine administration. Psychopharmacology 197, 83–94 (2008). https://doi.org/10.1007/s00213-007-1008-4
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DOI: https://doi.org/10.1007/s00213-007-1008-4