IV prenatal nicotine exposure increases the reinforcing efficacy of methamphetamine in adult rat offspring

Abstract

BackgroundMaternal smoking during pregnancy is correlated with increased substance use in offspring. Research using rodent models shows that gestational nicotine exposure produces enduring alterations in the neurodevelopment of motivational systems, and that rats prenatally treated with nicotine have altered motivation for drug reinforcement on fixed-ratio (FR) schedules of reinforcement. ObjectiveThe present study investigated methamphetamine (METH) self-administration in adult offspring prenatally exposed to intravenous (IV) nicotine or saline using a progressive-ratio (PR) schedule of reinforcement. MethodsPregnant rats were administered IV prenatal saline (PS) or nicotine (PN; 0.05mg/kg/infusion), 3×/day during gestational days 8–21. At postnatal day 70, offspring acquired a lever-press response for sucrose (26%, w/v; FR1-3). Rats were trained with METH (0.05mg/kg/infusion), and following stable FR responding, animals were tested using a progressive-ratio (PR) schedule for three different doses of METH (0.005, 0.025, and 0.05mg/kg/infusion). ResultsMETH infusion, active lever presses, and the ratio breakpoint are reported. PN-exposed animals exhibited more METH-maintained responding than PS controls, according to a dose×prenatal treatment interaction (e.g., infusions). PN rats self-administered more METH infusions between the range of 0.025 and 0.05, but not for the 0.005mg/kg/infusion dose. ConclusionsIV PN-exposure produced enhanced motivation to self-administer METH. These findings indicate that pregnant women who smoke tobacco may impart neurobiological changes in offspring's motivational systems that render them increasingly vulnerable to drug abuse during adulthood.