Chronic cocaine induces long-lasting neuro-adaptations within the mesocorticolimbic reward pathways (the motivational circuit) that are thought to underlie the manifestation of addictive behaviors. Recently, brain-derived neurotrophic factor (BDNF), within the NAcc and the ventral tegmental area (VTA), has emerged as a modulator of cocaine reward and reinstatement (Grimm et al. 2003; Hall et al. 2003; Horger et al, 1999; Lu et al. 2004). The cortico-striatal pathway from the prefrontal cortex (PFC) to the NAcc is critical in the manifestation of relapse behavior (Kalivas 2004; McFarland et al. 2003), and less is known about the role of BDNF neuro-transmission in this pathway following chronic cocaine. In the present study we will first examine BDNF protein expression within the motivational circuit following withdrawal from cocaine self-administration. Secondly, we will manipulate PFC neurotransmission by infusing BDNF directly into the PFC. We will then evaluate the enduring effects of intra-PFC BDNF infusions on reinstatement testing, TrkB receptor cell surface expression, and the phosphorylation state of the TrkB receptor, ERK, AKT, and PLCg, in the motivational circuit.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DA018500-01A2
Application #
7055563
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2006-05-01
Project End
2007-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
1
Fiscal Year
2006
Total Cost
$33,706
Indirect Cost
Name
Medical University of South Carolina
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
McGinty, Jacqueline F; Whitfield Jr, Timothy W; Berglind, William J (2010) Brain-derived neurotrophic factor and cocaine addiction. Brain Res 1314:183-93
Berglind, William J; Whitfield Jr, Timothy W; LaLumiere, Ryan T et al. (2009) A single intra-PFC infusion of BDNF prevents cocaine-induced alterations in extracellular glutamate within the nucleus accumbens. J Neurosci 29:3715-9