Offspring of Prenatal IV Nicotine Exposure Exhibit Increased Sensitivity to the Reinforcing Effects of Methamphetamine

Steven B. Harrod,Amanda J. Morgan,Ryan T. Lacy

doi:10.3389/fphar.2012.00116

Abstract

Maternal smoking during pregnancy is associated with increased substance abuse in offspring. Preclinical research shows that in utero exposure to nicotine, the primary psychoactive compound in tobacco smoke, influences the neurodevelopment of reward systems and alters motivated behavior in offspring. The present study determined if prenatal nicotine (PN) exposure altered the sensitivity to the reinforcing and aversive effects of methamphetamine (METH) in offspring using a low dose, intravenous (IV) exposure method. Pregnant dams were administered nicotine (0.05 mg/kg/injection) or prenatal saline (PS) 3×/day on gestational days 8–21, and adult offspring were tested using METH self-administration (experiment 1) or METH-induced conditioned taste aversion (CTA; experiment 2) procedures. For METH self-administration, animals were trained to respond for IV METH (0.05 mg/kg/infusion; fixed-ratio 3) and they were tested on varying doses of the reinforcer (0.0005–1.0 mg/kg/infusion). For METH CTA, rats received three saccharin and METH pairings (0, 0.3, or 0.5 mg/kg, sc) followed by 14 daily extinction trials. Experiment 1: PN and PS animals exhibited inverted U-shaped dose-response curves; however, the PN animal’s curve was shifted to the left, suggesting PN animals were more sensitive to the reinforcing effects of METH. Experiment 2: METH CTA was acquired in a dose-dependent manner and the factor of PN exposure was not related to the acquisition or extinction of METH-induced CTA. There were no sex differences in either experiment. These results indicate that IV PN-exposed adult offspring exhibited increased sensitivity to IV METH. This suggests that PN exposure, via maternal smoking, will alter the reinforcing effects of METH during later stages of development, and furthermore, will influence substance use vulnerability in adult human offspring.

Highlights

Maternal smoking during pregnancy imparts multiple health risks on the fetus (Castles et al, 1999; Ernst et al, 2001; Winzer-Serhan, 2008; Cornelius and Day, 2009)
LITTER PARAMETERS Data gathered from the prenatal nicotine (PN) and prenatal saline (PS)-exposed pups revealed no significant effect of prenatal treatment on the number of pups born, the ratio of male vs. female pups, righting reflex, negative geotaxis, or eye opening
These findings indicate that PN exposure did not disrupt postnatal development according to the ontogenetic measures used in the present study

Summary

Introduction

Maternal smoking during pregnancy imparts multiple health risks on the fetus (Castles et al, 1999; Ernst et al, 2001; Winzer-Serhan, 2008; Cornelius and Day, 2009). Multiple experiments demonstrate that PN exposure alone produces alterations in the neurodevelopment of the mesocorticolimbic dopamine (DA) system, which in part mediates motivated behavior Such PN-induced changes are hypothesized to mediate alterations in the behavioral repertoire of adolescent and adult offspring exposed to PN (Pauly et al, 2004; LeSage et al, 2006; Franke et al, 2008; Lacy et al, 2011). In drug self-administration experiments, adolescent offspring exposed to continuous PN acquired cocaine self-administration at a higher unit dose of drug relative to prenatal saline (PS) controls This finding suggests that PN exposure altered the reinforcing effects of cocaine (Franke et al, 2008).

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Conclusion