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A BDNF infusion into the medial prefrontal cortex suppresses cocaine seeking in rats

Berglind, William J., See, Ronald E., Fuchs, Rita A., Ghee, Shannon M., Whitfield, Timothy W., Miller, Scott W., McGinty, Jacqueline F.·2007·European Journal of Neuroscience

DOI 10.1111/j.1460-9568.2007.05692.x

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Abstract

The medial prefrontal cortex (mPFC) is critical for reinstatement of cocaine seeking and is the main source of brain‐derived neurotrophic factor (BDNF) to striatal regions of the brain relapse circuitry. To test the hypothesis that BDNF in the mPFC regulates cocaine‐seeking behavior, rats were trained to press a lever for cocaine infusions (0.2 mg/inf, 2 h/day) paired with light + tone conditioned stimulus (CS) presentations on 10 consecutive days. After the last self‐administration session, rats received a single infusion of BDNF (0.75 µg/0.5 µL/side) into the mPFC; this manipulation produced protracted effects on cocaine‐seeking behavior (non‐reinforced lever pressing). BDNF pretreatment administered after the last session attenuated cocaine seeking 22 h later and, remarkably, it also blocked cocaine‐induced suppression of phospho‐extracellular‐regulated kinase and elevated BDNF immunoreactivity in the nucleus accumbens. The same pretreatment also suppressed cocaine‐seeking behavior elicited by response‐contingent CS presentations after 6 days of forced abstinence or extinction training, as well as a cocaine challenge injection (10 mg/kg, i.p.) after extinction training. However, BDNF infused into the mPFC had no effect on food‐seeking behavior. Furthermore, BDNF infused on the sixth day of abstinence failed to alter responding, suggesting that the regulatory influence of BDNF is time limited. The suppressive effects of BDNF infused into the mPFC on cocaine seeking indicate that BDNF regulates cortical pathways implicated in relapse to drug seeking and that corticostriatal BDNF adaptations during early abstinence diminish compulsive drug seeking.

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Authors: Berglind, W. J., See, R. E., Fuchs, R. A., Ghee, S. M., Whitfield, T. W., Miller, S. W., & McGinty, J. F.
Affiliations: Medical University of South Carolina (US)
University of North Carolina at Chapel Hill (US)
ORCID: Fuchs, Rita A.
Miller, Scott W.
McGinty, Jacqueline F.
Venue: European Journal of Neuroscience
Publisher: Wiley
Published: 2007-08
Volume: 26
Issue: 3
Pages: 757-766
ISSN: 0953-816X (ISSN-L)
1460-9568
DOI: 10.1111/j.1460-9568.2007.05692.x
OpenAlex: W1917605014
Cited by: 187
References: 50
Citations by year: 2026: 1 · 2024: 4 · 2023: 1 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 11 · 2018: 16 · 2017: 7 · 2016: 16 · 2015: 8 · 2014: 16 · 2013: 20 · 2012: 19
FWCI: 4.91
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: European Journal of Neuroscience (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1c06rr015455-01a1)
National Institute on Drug Abuse (P50DA015369, P50 DA15369)
National Center for Research Resources (C06 RR-015455)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: brain-derived neurotrophic factor, medial prefrontal cortex, cocaine seeking, reinstatement, relapse, cocaine self-administration, conditioned stimulus, nucleus accumbens, extracellular signal-regulated kinase, forced abstinence, extinction, cocaine challenge, compulsive drug seeking, corticostriatal circuits
MeSH terms: Animals, Behavior, Animal, Cocaine, Conditioning, Psychological, Drug Administration Routes, Male, Neural Pathways, Nucleus Accumbens, Self Administration, Substance Withdrawal Syndrome, Time Factors, Rats, Sprague-Dawley, Prefrontal Cortex, Dopamine Uptake Inhibitors, Brain-Derived Neurotrophic Factor, Cocaine-Related Disorders, Extracellular Signal-Regulated MAP Kinases, Rats, Secondary Prevention

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A BDNF infusion into the medial prefrontal cortex suppresses cocaine seeking in rats

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