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Feb 16, 2010;1314 183-93.

Brain-derived neurotrophic factor and cocaine addiction.

Jacqueline F McGinty, Timothy W Whitfield, William J Berglind
Author Information
  1. Jacqueline F McGinty: Department of Neurosciences, Medical University of South Carolina, 173 Ashley Ave MSC 510, Charleston, SC 29425, USA. mcginty@musc.edu
PMID: 19732758 DOI: 10.1016/j.brainres.2009.08.078

Abstract

The effects of brain-derived neurotrophic factor (BDNF) on cocaine-seeking are brain region-specific. Infusion of BDNF into subcortical structures, like the nucleus accumbens and ventral tegmental area, enhances cocaine-induced behavioral sensitization and cocaine-seeking. Conversely, repeated administration of BDNF antiserum into the nucleus accumbens during chronic cocaine self-administration attenuates cocaine-induced reinstatement. In contrast, BDNF infusion into the dorsomedial prefrontal cortex immediately following a final session of cocaine self-administration attenuates relapse to cocaine-seeking after abstinence, as well as cue- and cocaine prime-induced reinstatement of cocaine-seeking following extinction. BDNF-induced alterations in the ERK-MAP kinase cascade and in prefronto-accumbens glutamatergic transmission are implicated in BDNF's ability to alter cocaine-seeking. Within 22 hours after infusion into the prefrontal cortex, BDNF increases BDNF protein in prefrontal cortical targets, including nucleus accumbens, and restores cocaine-mediated decreases in phospho-ERK expression in the nucleus accumbens. Furthermore, 3 weeks after BDNF infusion in animals with a cocaine self-administration history, suppressed basal levels of glutamate are normalized and a cocaine prime-induced increase in extracellular glutamate levels in the nucleus accumbens is prevented. Thus, BDNF may have local effects at the site of infusion and distal effects in target areas that are critical to mediating or preventing cocaine-induced dysfunctional neuroadaptations.

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Grants

  1. T32 DA007288/NIDA NIH HHS
  2. R01 DA003982/NIDA NIH HHS
  3. T32 DA007288-18/NIDA NIH HHS
  4. P50 DA015369-060006/NIDA NIH HHS
  5. R01 DA003982-16/NIDA NIH HHS
  6. F31 DA018500/NIDA NIH HHS
  7. F31 DA023743/NIDA NIH HHS
  8. R01 DA03982/NIDA NIH HHS
  9. T32 DA07288/NIDA NIH HHS
  10. P50 DA015369/NIDA NIH HHS

MeSH Term

Animals
Brain
Brain-Derived Neurotrophic Factor
Cocaine
Cocaine-Related Disorders
Dopamine Uptake Inhibitors
Glutamic Acid
Humans
MAP Kinase Signaling System
Nucleus Accumbens
Prefrontal Cortex

Chemicals

Brain-Derived Neurotrophic Factor
Dopamine Uptake Inhibitors
Glutamic Acid
Cocaine
Journal Article Research Support, N.I.H., Extramural Review
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Word Cloud

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