This application for a K02 Independent Scientist Award is submitted to enable me to devote additional time to research-related projects and foster my career in the field of opiate and stress research. I have recently received federal grant support from the National Institute on Drug Abuse (NIDA) (R0 I DA09082-05) for five years (2001-2006). The project entitled """"""""Opioid modulation of the coeruleo-cortical pathway"""""""" is a continuation of a project originally funded as an HRST Award by NIDA. The proposed studies involve collaborations with two other investigators in Philadelphia, Dr. Rita Valentino, a Professor at the Children's Hospital of Philadelphia and Dr. Michelle Page, a Research Assistant Professor at Hahnemann/Medical College of Pennsylvania.
The Specific Aims of the project integrate neuroanatomical approaches to provide cellular substrates for interactions between opioids and corticotropin releasing factor (CRF) that impact on noradrenergic neurons of the locus coeruleus (LC), neurophysiological approaches to identify the impact of CRF-opioid interactions on LC neuronal activity and neurochernical approaches to determine whether these interactions are translated to cortical targets. The guiding hypothesis is that stress engages CRF and opioid afferents to the LC that have opposing influences on this system. The balance between opioid and CRF influences may maintain the balance of active and passive coping behaviors in response to stress. Changes in LC sensitivity to either opioids (as a result of opioid tolerance) or CRF (as a result of prior stress) would shift this balance and the pattern of active vs. passive coping behaviors. These collaborative efforts would enable me to explore new techniques and experimental approaches. Moreover, collaborations with faculty within the Department of Pathology, Anatomy and Cell Biology at Thomas Jefferson University described in Aim 3 of the present proposal have been initiated to enhance my career development. Experiments include laser capture microdissection combined with microarray technology to examine differences in gene expression in LC neurons following exposure to opiates or swim stress. Appropriate training in the responsible conduct of research is also described within the application.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02DA015395-03
Application #
6779133
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Pilotte, Nancy S
Project Start
2002-08-15
Project End
2007-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
3
Fiscal Year
2004
Total Cost
$124,225
Indirect Cost
Name
Thomas Jefferson University
Department
Pathology
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Louboutin, J-P; Agrawal, L; Reyes, B A S et al. (2012) Gene delivery of antioxidant enzymes inhibits human immunodeficiency virus type 1 gp120-induced expression of caspases. Neuroscience 214:68-77
Louboutin, Jean-Pierre; Agrawal, Lokesh; Reyes, Beverly A S et al. (2010) HIV-1 gp120-induced injury to the blood-brain barrier: role of metalloproteinases 2 and 9 and relationship to oxidative stress. J Neuropathol Exp Neurol 69:801-16
Waselus, Maria; Nazzaro, Cristiano; Valentino, Rita J et al. (2009) Stress-induced redistribution of corticotropin-releasing factor receptor subtypes in the dorsal raphe nucleus. Biol Psychiatry 66:76-83
Scavone, Jillian L; Van Bockstaele, Elisabeth J (2009) Mu-opioid receptor redistribution in the locus coeruleus upon precipitation of withdrawal in opiate-dependent rats. Anat Rec (Hoboken) 292:401-11
Louboutin, Jean-Pierre; Agrawal, Lokesh; Reyes, Beverly A S et al. (2009) A rat model of human immunodeficiency virus 1 encephalopathy using envelope glycoprotein gp120 expression delivered by SV40 vectors. J Neuropathol Exp Neurol 68:456-73
Rudoy, Carla A; Reyes, Arith-Ruth S; Van Bockstaele, Elisabeth J (2009) Evidence for beta1-adrenergic receptor involvement in amygdalar corticotropin-releasing factor gene expression: implications for cocaine withdrawal. Neuropsychopharmacology 34:1135-48
Reyes, Beverly A S; Valentino, Rita J; Van Bockstaele, Elisabeth J (2008) Stress-induced intracellular trafficking of corticotropin-releasing factor receptors in rat locus coeruleus neurons. Endocrinology 149:122-30
Page, M E; Oropeza, V C; Van Bockstaele, E J (2008) Local administration of a cannabinoid agonist alters norepinephrine efflux in the rat frontal cortex. Neurosci Lett 431:1-5
Van Bockstaele, Elisabeth J; Qian, Yaping; Sterling, Robert C et al. (2008) Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain. Prog Neuropsychopharmacol Biol Psychiatry 32:1048-56
Reyes, B A S; Drolet, G; Van Bockstaele, E J (2008) Dynorphin and stress-related peptides in rat locus coeruleus: contribution of amygdalar efferents. J Comp Neurol 508:663-75

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