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

Calcium-dependent activator protein for secretion 2 (CAPS2; also referred to as CADPS2) is a dense core vesicle-associated protein that promotes the activity-dependent release of neuropeptides including neurotrophins. Addictive drugs appear to prime neurotrophin release in multiple brain regions, but mechanistic factors are still being elucidated. Here, experimenters administered cocaine to adolescent mice at doses that potentiated later cocaine self-administration. Experimenter-administered cocaine elevated the CAPS2 protein content in the orbitofrontal cortex (OFC; but not striatum) multiple weeks after drug exposure. Meanwhile, proteins that are sensitive to brain-derived neurotrophic factor (BDNF) release and binding (phosphorylated protein kinase B and phosphoinositide 3-kinase, and GABAAα1 levels) did not differ between cocaine-exposed and naive mice in the OFC. This pattern is consistent with evidence that CAPS2 primes stimulated release of neurotrophins like BDNF, rather than basal levels. Thus, cocaine administered at behaviorally relevant doses elevates CAPS2 protein content in the OFC, and the effects are detected long after cocaine exposure.