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 (Berl). 2008 Mar;197(1):83-94. doi: 10.1007/s00213-007-1008-4. Epub 2007 Nov 16.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Animals, Newborn
  • Arousal / drug effects
  • Arousal / physiology
  • Central Nervous System Stimulants / pharmacology*
  • Dextroamphetamine / pharmacology*
  • Dietary Fats / administration & dosage*
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Gestational Age
  • Lactation / physiology
  • Leptin / blood
  • Limbic System / drug effects
  • Limbic System / physiopathology*
  • Male
  • Mesencephalon / drug effects
  • Mesencephalon / physiopathology*
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • Neurons / drug effects
  • Neurons / physiology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiopathology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiopathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / physiology
  • Receptors, Dopamine D2 / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Tyrosine 3-Monooxygenase / metabolism
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / physiopathology

Substances

  • Central Nervous System Stimulants
  • Dietary Fats
  • Dopamine Plasma Membrane Transport Proteins
  • Leptin
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • 3,4-Dihydroxyphenylacetic Acid
  • Tyrosine 3-Monooxygenase
  • Dextroamphetamine
  • Dopamine