Dynamic BDNF activity in nucleus accumbens with cocaine use increases self-administration and relapse

Area of Science:

• Neuroscience
• Molecular Biology
• Addiction Research

Background:

• Cocaine use leads to addiction, but the underlying molecular mechanisms, particularly short-term gene regulation's long-term effects, remain unclear.
• Immediate early gene activation after cocaine exposure is transient, leaving its role in persistent behavioral changes largely unknown.

Purpose of the Study:

• To investigate the role of brain-derived neurotrophic factor (BDNF) and its signaling pathway in the nucleus accumbens (NAc) in the development and maintenance of cocaine addiction.
• To determine if dynamic BDNF regulation during cocaine self-administration influences subsequent drug-seeking behavior and relapse.

Main Methods:

• Rats underwent intravenous cocaine self-administration, followed by NAc infusions of BDNF or anti-BDNF antibodies.
• Localized inducible BDNF knockout was performed in mice using NAc-specific neuronal targeting.
• Cocaine self-administration, relapse behavior, and TrkB-mediated signaling were assessed.

Main Results:

• Cocaine self-administration transiently increased NAc BDNF and TrkB signaling.
• Augmenting NAc BDNF enhanced cocaine intake and relapse; neutralizing BDNF reduced intake and attenuated relapse.
• NAc neuronal BDNF was essential for maintaining elevated cocaine self-administration in mice.

Conclusions:

• Dynamic induction and release of BDNF from NAc neurons during cocaine use are critical for establishing and maintaining addictive behaviors.
• Targeting the BDNF pathway in the NAc may offer therapeutic strategies for cocaine addiction treatment.
• BDNF signaling in the NAc plays a pivotal role in the persistence of cocaine-induced behavioral changes.