My immediate goal is to establish myself as an independent researcher in the fields of neuroscience and cell biology, and obtain training in methods such as drug self-administration and animal behavior. For my long- term goals, I see myself as a faculty member in an academic environment with an established independent laboratory focusing on neuroscience and pursuing my interests in drug abuse and adult neurogenesis. Abuse of the psychostimulant methamphetamine has reached epidemic proportions and poses significant medical and social problems in the United States. Methamphetamine abuse in humans severely damages the prefrontal cortex and hippocampus, reducing cortical and hippocampal volume and producing memory deficits. Interestingly, adult precursor cell genesis has been demonstrated in the proliferative regions of the mammalian brain, namely, the medial prefrontal cortex (mPFC) and the hippocampal subgranular zone (SGZ). The newly born precursors mature into neurons or glia and are implicated in maintaining adult brain structure and function. While the devastating effects of methamphetamine on the structure and function of the RFC and hippocampus are becoming very clear, very little information exists on the affects of methamphetamine on adult gliogenesis and neurogenesis. The objective of this proposal is to investigate the mechanisms underlying methamphetamine self-administration-induced decrease in cell proliferation, gliogenesis and neurogenesis in the adult rat mPFC and hippocampus and to explore a possible relationship between methamphetmine-induced alterations in cortical and hippocampal structure and function. Importantly, we will use a clinically relevant self-administration paradigm of methamphetamine exposure to implement our specific aims. First, we will determine the harmful effects of methamphetamine escalation on cell proliferation and cell death over an escalation time course. Second, we will explore a possible mechanism for chronic methamphetamine-induced decrease in adult cortical and hippocampal gliogenesis and neurogenesis. Third, we will uncover the relationship between chronic methamphetamine- induced alteration in cell genesis and behavior. Taken together, our findings will improve our understanding of the complex mechanisms by which chronic exposure to psychostimulants affect adult brain function and may help generate better therapies to treat methamphetamine addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
3K01DA022473-05S1
Application #
8491946
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Pilotte, Nancy S
Project Start
2007-07-25
Project End
2013-06-30
Budget Start
2012-06-15
Budget End
2013-06-30
Support Year
5
Fiscal Year
2012
Total Cost
$13,500
Indirect Cost
$1,000
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Somkuwar, Sucharita S; Fannon, McKenzie J; Staples, Miranda C et al. (2016) Alcohol dependence-induced regulation of the proliferation and survival of adult brain progenitors is associated with altered BDNF-TrkB signaling. Brain Struct Funct 221:4319-4335
Sobieraj, Jeffery C; Kim, Airee; Fannon, McKenzie J et al. (2016) Chronic wheel running-induced reduction of extinction and reinstatement of methamphetamine seeking in methamphetamine dependent rats is associated with reduced number of periaqueductal gray dopamine neurons. Brain Struct Funct 221:261-76
Kim, Airee; Zamora-Martinez, Eva R; Edwards, Scott et al. (2015) Structural reorganization of pyramidal neurons in the medial prefrontal cortex of alcohol dependent rats is associated with altered glial plasticity. Brain Struct Funct 220:1705-20
Cohen, Ami; Soleiman, Matthew T; Talia, Reneta et al. (2015) Extended access nicotine self-administration with periodic deprivation increases immature neurons in the hippocampus. Psychopharmacology (Berl) 232:453-63
Galinato, M H; Orio, L; Mandyam, C D (2015) Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus. Neuroscience 286:97-108
Kim, Airee; Mandyam, Chitra D (2014) Methamphetamine affects cell proliferation in the medial prefrontal cortex: a new niche for toxicity. Pharmacol Biochem Behav 126:90-6
Contet, Candice; Kim, Airee; Le, David et al. (2014) μ-Opioid receptors mediate the effects of chronic ethanol binge drinking on the hippocampal neurogenic niche. Addict Biol 19:770-80
Engelmann, Alexander J; Aparicio, Mark B; Kim, Airee et al. (2014) Chronic wheel running reduces maladaptive patterns of methamphetamine intake: regulation by attenuation of methamphetamine-induced neuronal nitric oxide synthase. Brain Struct Funct 219:657-72
Deschaux, Olivier; Vendruscolo, Leandro F; Schlosburg, Joel E et al. (2014) Hippocampal neurogenesis protects against cocaine-primed relapse. Addict Biol 19:562-74
Recinto, Patrick; Samant, Anjali Rose H; Chavez, Gustavo et al. (2012) Levels of neural progenitors in the hippocampus predict memory impairment and relapse to drug seeking as a function of excessive methamphetamine self-administration. Neuropsychopharmacology 37:1275-87

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