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.
| 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 |
