Histamine H1 receptor occupancy by the new-generation antidepressants fluvoxamine and mirtazapine: a positron emission tomography study in healthy volunteers

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., 23 h) 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 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.