Our research focuses on effects of drugs on brain functions associated with attention and sensory gating (Mamiya et al 2005).  For example, we have discovered that nicotine acts to reduce the output of cholinergic neurons that play a crucial role in cortical activation.  This suggests that nicotine alters sensory processing by reducing the effects of novel stimuli.  At present a major foci of our research is the effects of maternal smoking on brainstem and hippocampal function.  We have found that cholinergic brainstem neurons in animals born to dams that were exposed to cigarette smoke during pregnancy exhibit increased excitability (Good et al 2006) and that gating of hippocampal responses is reduced by prenatal exposure (McLane, et al at Soc for Nicotine and Tobacco Res, 2005) .  We are also finding that significant changes in regional distributions of dopamine and 5-HT are associated with in utero exposure (McKeon et al, at Soc for Neuroscience, 2006).  These effects are present in prepubertal animals and persist throughout puberty and adulthood.  This suggests that maternal smoking is associated with significant and persistent alterations in basic brain functions that affect sensory processing.  Because it is well known that children born to mothers who smoked during pregnancy are more likely to engage in addictive behaviors as teens and adults, we are now investigating synergistic interactions between in utero exposure to the constituents of cigarette smoke and the effects of methamphetamine use during puberty.