Biphasic effect of abstinence duration following cocaine self-administration on spine morphology and plasticity-related proteins in prelimbic cortical neurons projecting to the nucleus accumbens core.

摘要: Cocaine self-administration (SA) in rats dysregulates glutamatergic signaling the prelimbic (PrL) cortex and glutamate release nucleus accumbens (NA) core, promoting cocaine seeking. PrL adaptations that affect relapse to drug seeking emerge during first week of abstinence, switching from an early (2 h) hypoglutamatergic state a later (7 days) hyperglutamatergic state. Different interventions normalize at each timepoint are necessary suppress relapse. We hypothesized plasticity-related proteins regulate neurotransmission as well dendritic spine morphology would be biphasically regulated these two phases abstinence cortical neurons projecting NA core (PrL–NA core). A combinatorial viral approach was used selectively label PrL–NA with mCherry fluorescent reporter. Male underwent 2 weeks SA or received yoked-saline infusions were perfused either 2 h 7 days after final session. Confocal microscopy 3D reconstruction analyses performed for Fos pCREB immunoreactivity (IR) layer V GluA1–IR GluA2–IR apical spines same neurons. Here, we show decreased head diameter, nuclear Fos–IR pCREB–IR, putative mushroom-type end SA, whereas opposite occurred following 1 week abstinence. Our findings reveal biphasic, duration-dependent alterations structural plasticity relapse-related pathway SA.