Consumption of Substances of Abuse during Pregnancy Increases Consumption in Offspring: Possible Underlying Mechanisms

Abstract

Correlative human observational studies on substances of abuse have been highly dependent on the use of rodent models to determine the neuronal and molecular mechanisms that control behavioral outcomes. This is particularly true for gestational exposure to non-illicit substances of abuse, such as excessive dietary fat, ethanol, and nicotine, which are commonly consumed in our society. Exposure to these substances during the prenatal period has been shown in offspring to increase their intake of these substances, induce other behavioral changes, and affect neurochemical systems in several brain areas that are known to control behavior. More importantly, emerging studies are linking the function of the immune system to these neurochemicals and ingestion of these abused substances. This review article will summarize the prenatal rodent models used to study developmental changes in offspring caused by prenatal exposure to dietary fat, ethanol, or nicotine. We will discuss the various techniques used for the administration of these substances into rodents and summarize the published outcomes induced by prenatal exposure to these substances. Finally, this review will cover some of the recent evidence for the role of immune factors in causing these behavioral and neuronal changes.

Keywords: inflammation; ingestive behavior; prenatal ethanol; prenatal fat; prenatal nicotine.

Figure 1

Cycle of substance exposure. The schematic depicts the current hypothesis of a simplified positive feedback loop involving prenatal exposure to substances of abuse that stimulate inflammatory systems. This inflammation may be involved in stimulating neuropeptides that further increase ingestive behavior, thus leading to a cyclical increase in exposure during the prenatal period with negative outcomes in the offspring.

Figure 2

Effects of prenatal HFD exposure on offspring brain. A schematic summarizing some of the changes that occur in the brains of offspring after being exposed to a HFD during gestation. GAL, galanin; ENK, enkephalin; OX, orexin; MCH, melanin-concentrating hormone; DA, dopamine; TH, tyrosine hydroxylase; MOR, μ-opioid receptor; CRF, corticotrophin releasing factor; BDNF, brain-derived neurotrophic factor; NGF, nerve growth factor.

Figure 3

Colocalization of CCR2 and enkephalin in hypothalamic neurons. Hypothalamic neurons extracted from chow-exposed embryos showing CCR2 to colocalize with the orexigenic peptide, enkephalin (orange). Scale: 25 μm. Green: enkephalin, red: CCR2, and blue: dapi.

Figure 4

Effects of prenatal ethanol exposure on offspring brain. A schematic summarizing some of the changes that occur in the brains of offspring after being exposed to low levels of ethanol during gestation. GAL, galanin; ENK, enkephalin; OX, orexin; MCH, melanin-concentrating hormone; CRF, corticotrophin releasing factor; ACTH, adrenocorticotropic hormone; DA, dopamine; GABA, γ-aminobutyric acid.

Figure 5

Effects of prenatal nicotine exposure on offspring brain. A schematic summarizing some of the changes that occur in the brains of offspring after being exposed to nicotine during gestation. GAL, galanin; ENK, enkephalin; OX, orexin; MCH, melanin-concentrating hormone; CRF, corticotrophin releasing factor; GCRs, glucocorticoid receptors; NPY, neuropeptide Y; AgRP, agouti-related protein; POMC, proopiomelanocortin; DA, dopamine; nAchRs, nicotinic acetylcholine receptors; GABA, γ-aminobutyric acid; GLUT, glutamate; BDNF, brain-derived neurotrophic factor.