Fostering itself increases nicotine self-administration in young adult male rats

Abstract

Rationale In gestational exposure studies, a fostered group is frequently used to control for drug-induced maternal effects. However, fostering itself has varying effects depending on the parameters under investigation Objectives This study was designed to assess whether maternal behavior contributed to enhanced acquisition (higher number of bar presses compared to controls) of nicotine self-administration (SA) displayed by offspring with gestational nicotine and ethanol (Nic+EtOH) exposure. Methods Offspring were exposed to Nic+EtOH throughout full gestation, that is, gestational days (GD) GD2-20 and during postnatal days 2-12 (PN2-12), the rodent third trimester-equivalent of human gestation during which rapid brain growth and synaptogenesis occur. Young adult (PN60) male offspring acquired operant nicotine SA, using a model of unlimited (i.e., 23h) access to nicotine. Results Gestational drug treatments did not alter litter parameters (body weight, volume distribution, crown-rump length, and brain weight) or postnatal growth of the offspring. Fostering increased locomotor activity to a novel environment on PN45 regardless of gestational treatment group. Surprisingly, fostering per se significantly increased the SA behavior of drug-naïve pair-fed (PF) controls, so that their drug taking behavior resembled the enhanced nicotine SA observed in non-fostered offspring exposed to Nic+EtOH during gestation. In contrast, fostering did not change the SA behavior of the Nic+EtOH group. Conclusions Fostering is shown to be its own experimental variable, ultimately increasing the acquisition of nicotine SA in control, drug-naïve offspring. As such, the current dogma that fostering is required for our gestationally drug-exposed offspring is contraindicated.

Investigating the influence of perinatal nicotine and alcohol exposure on the genetic profiles of dopaminergic neurons in the VTA using miRNA–mRNA analysis

“…4 were used for saline, 4 for alcohol, and 4 for nicotine-alcohol. Pups would be exposed to either alcohol or nicotine and alcohol for four weeks starting from gestational day 6 to postnatal day 14, equivalent to the three trimesters in human gestation during which rapid brain growth and synaptogenesis occur 38,49 . The central nervous system development of a rat at postnatal age of 7-14 days is suggested to correspond approximately to the human brain at term 134 .…”

“…Alcohol crosses from mother’s bloodstream through the placenta and directly enters into the unborn baby’s bloodstream, directly impacting the embryonic development of the fetus. Alcohol exposure throughout and after pregnancy over a period of 3‐trimester gestational exposure results in dysfunctional regulation of several neurotransmitters, including serotonin, glutamate, noradrenaline, acetylcholine, histamine, and dopamine 13 , 28 , 37 , 38 . Perinatal substance abuse does not only impact fetal brain development, resulting in behavioral disorders but also adult offspring exposed to nicotine during gestation self‐administer significantly more nicotine 28 , 39 , 40 .…”

Maternal immune activation: reporting guidelines to improve the rigor, reproducibility, and transparency of the model

“…The advantages of cross-fostering can be considered to partially control for a number of potential confounds in the MIA model such as litter size, sex ratio, lactation, and maternal behavior [147,153]. However, the exact procedures used for cross-fostering are often missing from publications, and fostering per se can introduce its own set of confounding factors [152,154,155]. To control for effects of handling and maternal-pup disruption in cross-fostering experiments, litters may be transferred between mothers within the same treatment groups (e.g., pups from an LPS-treated mother are switched to another LPS-treated mother).…”

Investigating the effects of chronic perinatal alcohol and combined nicotine and alcohol exposure on dopaminergic and non-dopaminergic neurons in the VTA

“…In this study, we have investigated the miRNome and transcriptome profiles of the rat pups which were perinatally exposed to alcohol or nicotine and alcohol combined and then compared by applying functional enrichment analysis among the DA and non-DA neurons of the VTA following exposures. Our well-established animal model 32 , 33 , 67 – 69 for perinatal nicotine exposure was used to expose dams to nicotine perinatally for four weeks, equivalent to the full term human pregnancy 19 , 70 – 73 . A Lieber-DeCarli ethanol diet was used to expose dams to alcohol throughout the four weeks, an established method which provides a high protein ethanol diet without introducing stress to the mother or compromising the mother’s health 74 , 75 .…”

“…Consumption of alcohol during pregnancy can cause many adverse immediate as well as long-term effects in the fetus, including fetal alcohol spectrum disorders (FASDs), preterm birth, stillbirth, poor coordination, learning disabilities, and neurobehavioral deficits 12 – 15 . Full-term pregnancy exposure to alcohol disrupts the regulation of neurotransmitters including dopamine (DA), serotonin, glutamate, noradrenaline, acetylcholine, and histamine 16 – 19 . Young postnatal rodents exposed to prenatal alcohol showed a familiarized response and enhanced preference to alcohol odor 20 – 29 .…”