This is a request for a renewal of a Research Scientist Award to allow me to continue to pursue the acquisition of techniques of molecular biology and neuroscience and to allow me to apply them to two NIDA funded research projects. Both projects are designed to test the hypothesis that Excitatory Amino Acid (EAA) receptors mediate the neuronal plasticity that is manifest as opioid tolerance and dependence or as certain types of nociceptive behavior. The first project will use NMDA and non-NMDA receptor antagonists and agonists as well as antisense or ribozymes targeted to NMDA receptors in selected animal behavioral paradigms to demonstrate the role of EAA receptors in opioid tolerance and nociception. Molecular and biochemical techniques will be used to identify and localize to neuroanatomical areas, the changes in gene expression that are associated with opioid tolerance or nociceptive behaviors. To complement and extend these approaches, opioid tolerance, dependence and nociceptive behaviors will be measured in knockout mice engineered with an absent or mutated EAA receptor. The second project will determine, in cultured cells expressing functional NMDA and opioid (mu or delta) receptors, the role of NMDA receptors in the changes that occur in opioid receptor signal transduction as a result of the exposure of these cells to opioids. The acquisition of molecular techniques, including, those related to gene targeting will be accomplished through sabbatical research in a laboratory where I can be directly involved in the design, production and evaluation of EAA receptor knockout mice. This RSA award will also allow me to maintain the reduction in teaching and administrative responsibilities that have for the past four years, significantly increased the time I can devote to enhancing my scientific skills.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Award (K05)
Project #
2K05DA000198-06
Application #
2829073
Study Section
Special Emphasis Panel (ZDA1-MXS-M (01))
Program Officer
Lin, Geraline
Project Start
1998-09-01
Project End
2003-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065
Schierberl, Kathryn; Hao, Jin; Tropea, Thomas F et al. (2011) Cav1.2 L-type Ca²? channels mediate cocaine-induced GluA1 trafficking in the nucleus accumbens, a long-term adaptation dependent on ventral tegmental area Ca(v)1.3 channels. J Neurosci 31:13562-75
Hunter, Deirtra A; Barr, Gordon A; Amador, Nicole et al. (2011) Estradiol-induced antinociceptive responses on formalin-induced nociception are independent of COX and HPA activation. Synapse 65:643-51
Hunter, Deirtra A; Barr, Gordon A; Shivers, Kai-Yvonne et al. (2011) Interactions of estradiol and NSAIDS on carrageenan-induced hyperalgesia. Brain Res 1382:181-8
Gregus, Ann M; Tropea, Thomas F; Wang, Yanran et al. (2010) Deletion of the GluR5 subunit of kainate receptors affects cocaine sensitivity and preference. Neurosci Lett 468:186-9
Weyerbacher, Amanda R; Xu, Qinghao; Tamasdan, Cristina et al. (2010) N-Methyl-D-aspartate receptor (NMDAR) independent maintenance of inflammatory pain. Pain 148:237-46
Gregus, A M; Inra, C N; Giordano 3rd, T P et al. (2010) Spinal mediators that may contribute selectively to antinociceptive tolerance but not other effects of morphine as revealed by deletion of GluR5. Neuroscience 169:475-87
Bogulavsky, Johanna J; Gregus, Ann M; Kim, Paul T-H et al. (2009) Deletion of the glutamate receptor 5 subunit of kainate receptors affects the development of morphine tolerance. J Pharmacol Exp Ther 328:579-87
Garraway, Sandra M; Xu, Qinghao; Inturrisi, Charles E (2009) siRNA-mediated knockdown of the NR1 subunit gene of the NMDA receptor attenuates formalin-induced pain behaviors in adult rats. J Pain 10:380-90
Xu, Qinghao; Garraway, Sandra M; Weyerbacher, Amanda R et al. (2008) Activation of the neuronal extracellular signal-regulated kinase 2 in the spinal cord dorsal horn is required for complete Freund's adjuvant-induced pain hypersensitivity. J Neurosci 28:14087-96
Glass, Michael J; Hegarty, Deborah M; Oselkin, Martin et al. (2008) Conditional deletion of the NMDA-NR1 receptor subunit gene in the central nucleus of the amygdala inhibits naloxone-induced conditioned place aversion in morphine-dependent mice. Exp Neurol 213:57-70

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