The Role of NMDA Receptor Antagonists in Nicotine Tolerance, Sensitization, and Physical Dependence: A Preclinical Review

Jain, Raka; Mukherjee, Kaushiki; Balhara, Yatan Pal Singh

doi:10.3349/ymj.2008.49.2.175

Cited by 26 publications

(28 citation statements)

References 134 publications

(149 reference statements)

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“…In support of this hypothesis, our data also revealed that intra-CA1 microinjection of MK-801 reversed the NMDA response on the improving effect of nicotine in ethanol-induced amnesia. There are reports indicating that nicotinic and glutamate systems have direct interactions (for review see Jain et al 2008). In some other studies, the inhibitory effects of MK-801 on the behavioral effects of nicotine have been shown.…”

Section: Discussionmentioning

confidence: 97%

“…Considering that nicotine increases the glutamatergic synaptic transmission in the hippocampus by activation of presynaptic nicotinic receptors (Wonnacott 1997) and has extensive functional interaction with NMDA receptors (Jain et al 2008), the present study attempts to determine the possible role of NMDA receptors of the dorsal hippocampus in nicotine's effects on memory impairment by ethanol administration.…”

Section: Introductionmentioning

confidence: 99%

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Nicotine improves ethanol-induced memory impairment: The role of dorsal hippocampal NMDA receptors

et al. 2010

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Nicotine improves ethanol-induced memory impairment: The role of dorsal hippocampal NMDA receptors

et al. 2010

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“…Early on, most researchers focused on the mesolimbic dopamine system and they established that dopamine and dopamine receptors (DRs) play a key role in neurobiological mechanisms of addiction [29,30]. However, experiments have increasingly suggested that glutamate receptors, especially NMDARs, also contribute to neurobiological changes of addiction to psychomotor stimulants [9,10]. Building on these previous findings, we used ifenprodil, a selective antagonist of the GluN2B subunit, to explore the role of GluN2B-containing NMDARs in METH-induced behavioral sensitization and potential downstream signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…N-Methyl-d-aspartate receptors (NMDARs), a kind of glutamate receptor, have been frequently reported to participate in psychomotor stimulants-induced behavioral sensitization [9,10]. Functional NMDARs contain heteromeric combinations of the GluN1 subunit and various subunits of the GluN2 subfamily [11].…”

Section: Locomotionmentioning

confidence: 99%

Ifenprodil Attenuates Methamphetamine-Induced Behavioral Sensitization and Activation of Ras-ERK-∆FosB Pathway in the Caudate Putamen

Liu

Qiao

et al. 2016

Neurochem Res

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Addiction is a debilitating, chronic psychiatric disorder that is difficult to cure completely owing to the high rate of relapse. Behavioral sensitization is considered to may underlie behavioral changes, such as relapse, caused by chronic abuse of psychomotor stimulants. Thus, its animal models have been widely used to explore the etiology of addiction. Recently, increasing evidence has demonstrated that N-methyl-D-aspartate receptors (NMDARs) play an important role in addiction to psychomotor stimulants. However, the role of GluN2B-containing receptors and their downstream signaling pathway(s) in behavioral sensitization induced by methamphetamine (METH) have not been investigated yet. In this study, we used different doses of ifenprodil (2.5, 5, 10 mg/kg), a selective antagonist of the GluN2B subunit, to investigate the role of GluN2B-containing NMDARs in METH-induced behavioral sensitization. We then examined changes in the levels of Ras, phosphorylated extracellular signal-regulated kinase (pERK)/ERK, and ∆FosB in the caudate putamen (CPu) by western blot. We found that 2.5 or 10 mg/kg ifenprodil significantly attenuated METH-induced behavioral sensitization, whereas the mice treated with a moderate dose of ifenprodil (5 mg/kg) displayed no significant changes. Further results of western blot experiments showed that repeated administration of METH caused the increases in the levels of Ras, pERK/ERK and ∆FosB in the CPu, and these changes were inhibited by only the 2.5 mg/kg dose of ifenprodil. In conclusion, these results demonstrated that 2.5 mg/kg ifenprodil could attenuate METH-induced behavioral sensitization. Moreover, GluN2B-containing NMDARs and their downstream Ras-ERK-∆FosB signaling pathway in the CPu might be involved in METH-induced behavioral sensitization.

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“…The role that NMDA receptors play in the mesocorticolimbic reward pathway has long been recognized (Jain et al 2008;Mansvelder et al 2003;Zellner and Ranaldi 2010). We previously demonstrated that VTA glutamate release induced by nicotine is correlated with accumbal DA release in untreated rats (Fu et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Full-Gestational Exposure to Nicotine and Ethanol Results in Long-Term Dysregulation in the Ventral Tegmental Area

Roguski¹

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DEDICATIONI dedicate this work in memory of my father George F. Roguski for instilling in me the importance of hard work to achieve your goals and all the years of unconditional love and support.I also dedicate my dissertation work in memory my mentor Dr. Shannon G. Matta for all her hours of reflecting, reading, encouraging, and patience. Most of all for taking a chance on me and helping me further my education.iv ACKNOWLEDGEMENTS I wish to thank my committee members who were more than generous with their expertise and precious time. A special thanks to Dr. Jeff Steketee, my committee chairman for always being there for help when need and most importantly for stepping in to help me finish. I would also like to thank Dr. Burt M Sharp for always having extra time throughout all my years at UT. Thank you Dr. Andrea J Elberger, Dr. Edwards A Park, and Dr. Steve Tavalin for agreeing to serve on my committee.I would like to thank the University of Tennessee Health Science Center Neuroscience Institute for their support over the years.Thank you to Dr. Hao Chen for teaching me every technique used in my experiments. I truly would not have been able to accomplish these experiments without your help.Finally, to my Mum, Alex, and Bobbi Jo thank you for being there at any time and the love and support over the years.v ABSTRACT Nicotine is considered a gateway drug for other drugs of abuse. The majority of smokers that begin smoking in adolescence, continue into adulthood. Multiple factors have been linked with smoking initiation, including maternal smoking. Drug exposure during pregnancy has long been suspected to exert deleterious effects on the fetal brain. Concurrent use of smoking and drinking alcohol throughout pregnancy is an all too frequent occurrence in the human population especially in disadvantaged and younger women.The present study investigated the potential contributing factors for the enhanced nicotine self-administration as seen in offspring with gestational exposure to nicotine and ethanol (Nic+EtOH).* We focused on the mesocorticolimbic pathway, specifically the λ-aminobutyric acid (GABA) and glutamate modulators of ventral tegmental area (VTA) dopamine (DA) neurons that project to the nucleus accumbens (NAcc).Our animal model of full gestational exposure to Nic+EtOH exposes the developing brain to both drugs throughout the entire 3 trimester human equivalent [i.e. gestational days (GD) 1-22 and postnatal days (PN) 2-12]. Using self-administration (SA), in vivo microdialysis, quantitative PCR, and western blot analysis, we investigated alterations in the VTA of offspring.We found that the enhancement of nicotine SA acquisition of offspring with gestational Nic+EtOH exposure is not due to changes in maternal-pup interactions. The offspring with gestational Nic+EtOH exposure have a dramatic change in neurotransmitter release in response to 30µg i.v. nicotine; that displays a 75% increase of NAcc DA and a 50% reduction of VTA GABA release. In comparison, pair-fed (PF) offspring show a 20% increase in NAcc D...

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The Role of NMDA Receptor Antagonists in Nicotine Tolerance, Sensitization, and Physical Dependence: A Preclinical Review

Cited by 26 publications

References 134 publications

Nicotine improves ethanol-induced memory impairment: The role of dorsal hippocampal NMDA receptors

Nicotine improves ethanol-induced memory impairment: The role of dorsal hippocampal NMDA receptors

Ifenprodil Attenuates Methamphetamine-Induced Behavioral Sensitization and Activation of Ras-ERK-∆FosB Pathway in the Caudate Putamen

Full-Gestational Exposure to Nicotine and Ethanol Results in Long-Term Dysregulation in the Ventral Tegmental Area

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