For example, the dose of methamphetamine used in the present experiment (0.3 mg/kg) may have produced a rapid acquisition of behavioral sensitization, because the sensitized response was exhibited as a 9% increase over that of the acute response. saline or methamphetamine (0.3 mg/kg) and locomotor activity was measured after the first and seventh injections. On PND 36, brains were removed, flash frozen, and BDNF protein levels in the nucleus accumbens (NAcc), dorsal striatum (Str), frontal cortex (FC), and hippocampus (Hipp) were analyzed. GN did not affect habituation or the induction of methamphetamine-induced sensitization. Interestingly, GN, but not adolescent methamphetamine treatment, elevated levels of BDNF in the NAcc and Str; however, the GN-induced increase in BDNF in the FC was attenuated by adolescent methamphetamine treatment. Both GN and adolescent methamphetamine treatment increased BDNF in the Hipp. These findings indicate that GN exposure will result in increased levels of BDNF protein throughout the mesocorticolimbic dopamine system during adolescent development, and suggests that methamphetamine abuse will modulate the expression of BDNF in motivational circuitries of adolescent offspring exposed to GN. Keywords:Gestational nicotine, adolescence, methamphetamine, locomotor activity, BDNF == Introduction == Maternal tobacco smoking during pregnancy is associated with enduring psychopathology in offspring. Neurobehavioral disorders, such as conduct disorder (Corneliuset al., 2007;Fergussonet al., 1998;Stene-Larsenet al., 2009), attention deficit hyperactivity disorder (Buttonet al., 2007;Thaparet al., 2003), and material use disorder (SUD;Bukaet al., 2003;Kandelet al., 1994;Weissmanet al., 1999), are observed in gestational tobacco smoke-exposed offspring at a higher incidence than non-exposed individuals. Maternal tobacco smoking thus increases the vulnerability to neurodevelopmental disorders in offspring that are manifest during adolescent development. The neural substrates affected by maternal smoke exposure, which also contribute to these enduring maladaptive behaviors, however, are not well comprehended. The influence of prenatal nicotine exposure on offspring development, apart from other constituents in tobacco smoke, has been investigated with rodent models of gestational nicotine (GN) exposure. This BMS-911543 research clearly shows that nicotine delivered during gestation has teratogenic effects on neurodevelopment (Dwyeret al., 2008;Slotkin, 1998). Contemporary models administer nicotine either constantly via a subcutaneous osmotic minipump (Dwyeret al., 2008;Slotkin, 1998); orally through drinking water (Paulyet al., 2004;Zhuet al., 1996), or intravenously (Lacyet al., 2011;LeSageet al., 2006). Studies utilizing the continuous route have exhibited that nicotine exposure during the gestational period alters cell replication, cell survival, and synaptogenesisin utero,relative to saline-treated animals (GS;Navarroet al., 1989;Slikkeret al., 2005;Slotkin, 2004). Moreover, GN produced neurodevelopmental alterations in the mesocorticolimbic dopamine (DA) system, which, in part, mediates motivated behavior (Edwards and Koob, 2010;Everittet al., 2008;Kalivas, 2009;Robinson and Berridge, 2003;Wise and Bozarth, 1987). Thus, continuous GN exposure altered DA neurons in fetal (Navarroet al., 1989;Ribary and Lichtensteiger, 1989) and preweanling rats (Muneokaet al., 1997) and resulted in decreased DA concentrations and D2 receptors in the striatum of weanlings (Richardson and Tizabi, 1994). Adolescent offspring exhibited increased c-fosexpression in the infralimbic cortex and nucleus accumbens (NAcc) core (Parket al., 2006) and decreased nicotine-evoked DA release in the NAcc shell, relative to GS controls (Kaneet al., 2004). These findings indicate that continuous GN exposure produces long-lasting changes in the activity of neurons that comprise the motivational system, and demonstrate that nicotine alone produces long-lasting neurobiological changes that may contribute to the psychopathology observed in offspring exposed BMS-911543 to prenatal tobacco smoke. That GN produces increased neuronal activity in brain areas that are known to mediate reward and motivation suggests other neurobiological alterations, such as increases in activity-dependent neurotrophic factors, may also change as a result of prenatal nicotine exposure (Kaneet al., 2004;Parket al., 2006). Neurotrophic factors aid in the proliferation, differentiation and survival of neurons (Thoenen, 1995), and are known to play a role in motivated behavior (Thomaset al., 2008). For example, brain derived neurotrophic factor (BDNF) is important for synaptic plasticity and the survival of mesocorticolimbic DA neurons (Hymanet al., 1991), and microinfusion of BDNF into the ventral tegmental area altered cocaine-induced changes in locomotor behavior (Horgeret al., 1999). A novel hypothesis is usually that GN exposure alters expression of BDNF protein in the mesocorticolimbic dopamine system of developing offspring. An enduring influence of abused drugs such as amphetamine, cocaine, and nicotine, on BDNF protein and BDNF mRNA expression has been demonstrated. For example, postnatal amphetamine exposure has been shown to decrease protein levels of BDNF in the occipital cortex and hypothalamus (Angelucciet al., 2007;Banerjeeet al., 2009), and in contrast, cocaine or BMS-911543 nicotine treatment has been shown to increase BDNF in the cortex, striatum, and NAcc, (Correllet Rabbit Polyclonal to POLE4 al., 2009;Grahamet al., 2007;Maggioet al., 1998). Second,Weiet al.(2011)characterized numerous potential cell survival and cell death pathways associated with continuous GN exposure in adolescent offspring. Gestational nicotine was shown to result in greater mRNA expression of survival related growth factors, including BDNF, in the NAcc of adolescent offspring. In addition, increased expression of BDNF mRNA was observed in the striatum, whereas the prefrontal cortex showed no change in growth factors. These results are consistent.