Faculty Collaboration Database

Accumbens brain-derived neurotrophic factor (BDNF) transmission inhibits cocaine seeking. Addict Biol 2019 Sep;24(5):860-873

Date

06/12/2018

Pubmed ID

29890020

Pubmed Central ID

PMC8320750

DOI

10.1111/adb.12638

Scopus ID

2-s2.0-85069485559 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

Brain-derived neurotrophic factor (BDNF) regulates a variety of physiological processes, and several studies have explored the role of BDNF in addiction-related brain regions like the nucleus accumbens core (NAcore). We sought to understand the rapid effects of endogenous BDNF on cocaine seeking. Rats were trained to self-administer cocaine and extinguished. We then microinjected two inhibitors of BDNF stimulation of tropomyosin receptor kinase B (TrkB), the non-competitive receptor antagonist ANA-12 and TrkB/Fc, a fusion protein that binds BDNF and prevents TrkB stimulation. Blocking TrkB or inactivating BDNF in NAcore potentiated active lever pressing, showing that endogenous BDNF tone was present and supplying inhibitory tone on cue-induced reinstatement. To determine if exogenous BDNF also negatively regulated reinstatement, BDNF was microinjected into NAcore 15 minutes before cue-induced reinstatement. BDNF decreased cocaine seeking through TrkB receptor binding, but had no effect on inactive lever pressing, spontaneous or cocaine-induced locomotion, or on reinstated sucrose seeking. BDNF-infusion potentiated within trial extinction when microinjected in the NAcore during cue- and context + cue induced reinstatement, and the inhibition of lever pressing lasted at least 3 days post injection. Although decreased reinstatement endured for 3 days when BDNF was administered prior to a reinstatement session, when microinjected before an extinction session or in the home cage, BDNF did not alter subsequent cued-reinstatement. Together, these data show that endogenous BDNF acts on TrKB to provide inhibitory tone on reinstated cocaine seeking, and this effect was recapitulated by exogenous BDNF.

Author List

Bobadilla AC, Garcia-Keller C, Chareunsouk V, Hyde J, Medina Camacho D, Heinsbroek JA, Kalivas PW

Author

Constanza Garcia Keller PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Analysis of Variance
Animals
Azepines
Benzamides
Brain-Derived Neurotrophic Factor
Cocaine
Cocaine-Related Disorders
Cues
Dopamine Uptake Inhibitors
Drug-Seeking Behavior
Male
Motor Activity
Nucleus Accumbens
Rats, Sprague-Dawley
Receptor, trkB
Reinforcement Schedule
Self Administration
Sucrose
Sweetening Agents