Gestational IV nicotine produces elevated brain-derived neurotrophic factor in the mesocorticolimbic dopamine system of adolescent rat offspring

Maternal smoking during pregnancy is associated with enduring psychopathology, such as increased likelihood of substance use, in offspring. Various animal models demonstrate that continuous nicotine exposure produces teratogenic effects in offspring, as well. In this experiment, a novel intravenous...

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Published in:Synapse (New York, N.Y.) N.Y.), 2011-12, Vol.65 (12), p.1382-1392
Main Authors: Harrod, Steven B., Lacy, Ryan T., Zhu, Jun, Hughes, Benjamin A., Perna, Marla K., Brown, Russell W.
Format: Article
Language:English
Subjects:
Adolescence
Aging - drug effects
Aging - physiology
Amphetamine-Related Disorders - etiology
Amphetamine-Related Disorders - metabolism
Amphetamine-Related Disorders - physiopathology
Animal models
Animals
Animals, Newborn
BDNF
Brain-derived neurotrophic factor
Brain-Derived Neurotrophic Factor - biosynthesis
Brain-Derived Neurotrophic Factor - metabolism
Cortex (frontal)
Dams
Disease Models, Animal
Dopamine
Dopamine - physiology
Dopamine Uptake Inhibitors - pharmacology
Drug abuse
Female
gestational nicotine
Habituation
Intravenous administration
Locomotor activity
Male
Methamphetamine
Neostriatum
Nicotine
Nicotine - pharmacology
Nucleus accumbens
Pregnancy
Prenatal Exposure Delayed Effects - chemically induced
Prenatal Exposure Delayed Effects - metabolism
Prenatal Exposure Delayed Effects - physiopathology
Progeny
Psychopathology
Rats
Rats, Sprague-Dawley
Synapses
Teratogenicity
Tobacco Use Disorder - complications
Tobacco Use Disorder - metabolism
Tobacco Use Disorder - physiopathology
Ventral Tegmental Area - drug effects
Ventral Tegmental Area - growth & development
Ventral Tegmental Area - metabolism
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Summary:Maternal smoking during pregnancy is associated with enduring psychopathology, such as increased likelihood of substance use, in offspring. Various animal models demonstrate that continuous nicotine exposure produces teratogenic effects in offspring, as well. In this experiment, a novel intravenous (IV) exposure model was used to determine if gestational nicotine (GN) treatment produced alterations in methamphetamine‐induced sensitization and the expression of brain‐derived neurotrophic factor (BDNF) in the mesocorticolimbic dopamine (DA) system of adolescent offspring. Dams were injected with IV saline or nicotine (0.05 mg/kg/injection) three times per day on gestational days 8–21. Habituation was measured on postnatal day (PND) 25–27 and baseline activity on PND 28. On PND 29–35, offspring were injected with 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 DA system during adolescent development and suggests that methamphetamine abuse will modulate the expression of BDNF in motivational circuitries of adolescent offspring exposed to GN. Synapse, 2011. © 2011 Wiley‐Liss, Inc.
ISSN:0887-4476
1098-2396
1098-2396
DOI:10.1002/syn.20975