Maternal cigarette smoking is a major public health problem in the United States. Overall, approximately 20% of women in the US are regular cigarette smokers. Only 30% of US women who abuse tobacco quit smoking when they find out they are pregnant. Epidemiological studies indicate that children of mothers who smoke -10 cigarettes a day throughout gestation exhibit increased vulnerability for substance abuse disorder. Currently, little is known about the neurobehavioral mechanisms through which prenatal nicotine (NIC) exposure renders offspring of maternal smokers more vulnerable to substance abuse. The proposed program of research will test the hypothesis that repeated, prenatal IV NIC will alter normal mesocorticolimbic DA function during gestation, thereby altering the locomotor, reinforcing, and rewarding effects of METH or COC in adulthood. The proposed mechanism of subsequent psychostimulant-induced behavioral alterations is dopaminergic. First, the dose dependent effects of prenatal NIC on the induction, and expression, of intravenous (IV) methamphetamine (METH) or cocaine (COC)-induced behavioral sensitization in adult female and male rats will be determined. We have found that maternal smoke exposure (putatively NIC) produced increased COC-induced hyperactivity in female offspring. Second, we will determine the changes in DA receptors and DA transporters in adult male and female rats prenatally exposed to NIC and behaviorally sensitized to IV METH or COC to establish a mechanism of action. Third, the effects of prenatal NIC on the relative reinforcement and reward produced by IV METH or COC in adult female and male rats will be determined. The long-term programmatic goal of the present research proposal is to elucidate the neurobiological mechanisms that render people exposed to in utero NIC more vulnerable to substance abuse. The IV model of prenatal NIC exposure, in combination with contemporary methods to assess drug related behaviors, is innovative and will be translational to the health issues of drug abuse and the neurological complications that result from maternal smoking. The ultimate goal of this research is to develop drug prevention strategies and pharmacotherapies to decrease vulnerability to drug abuse. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA021287-02
Application #
7408114
Study Section
Special Emphasis Panel (ZRG1-BBBP-J (02))
Program Officer
Hoffman, Allison
Project Start
2007-04-15
Project End
2012-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
2
Fiscal Year
2008
Total Cost
$246,960
Indirect Cost
Name
University of South Carolina at Columbia
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
041387846
City
Columbia
State
SC
Country
United States
Zip Code
29208
Lacy, Ryan T; Brown, Russell W; Morgan, Amanda J et al. (2016) Intravenous Prenatal Nicotine Exposure Alters METH-Induced Hyperactivity, Conditioned Hyperactivity, and BDNF in Adult Rat Offspring. Dev Neurosci 38:171-185
Moran, Landhing M; Hord, Lauren L; Booze, Rosemarie M et al. (2016) The role of sensory modality in prepulse inhibition: An ontogenetic study. Dev Psychobiol 58:211-22
Gomez, Adrian M; Sun, Wei-Lun; Midde, Narasimha M et al. (2015) Effects of environmental enrichment on ERK1/2 phosphorylation in the rat prefrontal cortex following nicotine-induced sensitization or nicotine self-administration. Eur J Neurosci 41:109-19
Lacy, Ryan T; Morgan, Amanda J; Harrod, Steven B (2014) IV prenatal nicotine exposure increases the reinforcing efficacy of methamphetamine in adult rat offspring. Drug Alcohol Depend 141:92-8
Morgan, Amanda J; Harrod, Steven B; Lacy, Ryan T et al. (2013) Intravenous prenatal nicotine exposure increases orexin expression in the lateral hypothalamus and orexin innervation of the ventral tegmental area in adult male rats. Drug Alcohol Depend 132:562-70
Lacy, Ryan T; Hord, Lauren L; Morgan, Amanda J et al. (2012) Intravenous gestational nicotine exposure results in increased motivation for sucrose reward in adult rat offspring. Drug Alcohol Depend 124:299-306
Midde, Narasimha M; Gomez, Adrian M; Harrod, Steven B et al. (2011) Genetically expressed HIV-1 viral proteins attenuate nicotine-induced behavioral sensitization and alter mesocorticolimbic ERK and CREB signaling in rats. Pharmacol Biochem Behav 98:587-97
Horton, David B; Siripurapu, Kiran B; Norrholm, Seth D et al. (2011) meso-Transdiene analogs inhibit vesicular monoamine transporter-2 function and methamphetamine-evoked dopamine release. J Pharmacol Exp Ther 336:940-51
Mactutus, Charles F; Harrod, Steven B; Hord, Lauren L et al. (2011) Prenatal IV Cocaine: Alterations in Auditory Information Processing. Front Psychiatry 2:38
Harrod, Steven B; Lacy, Ryan T; Zhu, Jun et al. (2011) Gestational IV nicotine produces elevated brain-derived neurotrophic factor in the mesocorticolimbic dopamine system of adolescent rat offspring. Synapse 65:1382-92

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