Cocaine Elevates Calcium-Dependent Activator Protein for Secretion 2 in the Mouse Orbitofrontal Cortex

Area of Science:

• Neuroscience
• Molecular Biology
• Addiction Research

Background:

• Calcium-dependent activator protein for secretion 2 (CAPS2) facilitates neuropeptide release, including neurotrophins.
• Addictive drugs may prime neurotrophin release, but the underlying mechanisms require further investigation.

Purpose of the Study:

• To investigate the long-term effects of cocaine exposure on CAPS2 protein levels in adolescent mice.
• To explore the relationship between cocaine-induced CAPS2 changes and neurotrophin signaling.

Main Methods:

• Adolescent mice received cocaine, followed by behavioral assessment of self-administration.
• CAPS2 protein levels were measured in the orbitofrontal cortex (OFC) and striatum weeks after cocaine exposure.
• Levels of BDNF-sensitive proteins (p-Akt, p-PI3K, GABAAα1) were assessed in the OFC.

Main Results:

• Cocaine administration potentiated later cocaine self-administration.
• Elevated CAPS2 protein content was observed in the OFC, but not the striatum, weeks post-cocaine exposure.
• No significant differences in BDNF-sensitive proteins were found between cocaine-exposed and naive mice in the OFC.

Conclusions:

• Cocaine exposure at behaviorally relevant doses increases CAPS2 protein in the OFC long after drug cessation.
• This suggests CAPS2 plays a role in priming stimulated neurotrophin release, potentially contributing to long-term addiction-related changes.