title: Maternal high-fat intake alters presynaptic regulation of dopamine in the nucleus accumbens and increases motivation for fat rewards in the offspring.
abstract: High caloric intake during early postnatal development can have long term consequences for the offspring. We previously reported that the adult offspring of dams fed a high-fat diet during the last week of gestation and throughout lactation display blunted locomotor response to amphetamine (AMP) and reduced sensitization to the drug compared to offspring of control diet dams. Here, we report that the subsensitivity of high-fat offspring to AMP's locomotor stimulant action reflects, at least in part, altered regulation of nucleus accumbens (NAc) dopamine (DA) transmission. When compared to controls, the DA response of high-fat animals to AMP, as measured with microdialysis, was attenuated in the NAc, but unaffected in the prefrontal cortex (PFC). A relatively higher activity of NAc synaptosomal DA transporter sites without changes in vesicular monoamine transporter (VMAT) uptake capacity was also observed in high-fat offspring. Moreover, ventral tegmental area (VTA) D(2) receptor mRNA levels were decreased in high-fat offspring, suggesting a reduction in DA release-regulating D(2) autoreceptors in terminal regions such as the NAc. The magnitude of locomotor response to D(2/3) receptor activation (with quinpirole) was greater in high-fat than in control animals despite having comparable postsynaptic D(2) mRNA levels in the NAc. Finally, while operant responding for a sugar-enriched food reward did not differ between diet groups, high-fat offspring displayed increased operant responding for a fat-enriched reward compared to controls. These findings add to mounting evidence that early life exposure to elevated dietary maternal fat can lead to long lasting changes in DA-mediated behavioral responses to stimulant drugs and fat-enriched foods.
authors.affiliation: McGill University, Department of Psychiatry and Douglas Mental Health University Institute, 6875 Lasalle Boulevard, Montreal, Quebec H4H 1R3, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Naef
authors.forename: L
authors.initials: L
authors.lastname: Moquin
authors.forename: G
authors.initials: G
authors.lastname: Dal Bo
authors.forename: B
authors.initials: B
authors.lastname: Giros
authors.forename: A
authors.initials: A
authors.lastname: Gratton
authors.forename: C-D
authors.initials: CD
authors.lastname: Walker
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003216:Conditioning, Operant; D004032:Diet; D004041:Dietary Fats / Q000009:adverse effects*; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D017403:In Situ Hybridization; D008297:Male; D017551:Microdialysis; D009042:Motivation / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000032:analysis / Q000378:metabolism; D012201:Reward; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D050493:Vesicular Monoamine Transport Proteins / Q000032:analysis / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D011954:Receptors, Dopamine; D050493:Vesicular Monoamine Transport Proteins; D000661:Amphetamine; D004298:Dopamine