Heroin Self-Administration and Extinction Increase Prelimbic Cortical Astrocyte–Synapse Proximity and Alter Dendritic Spine Morphometrics That Are Reversed by N-Acetylcysteine

Clinical and preclinical studies indicate that adaptations in corticostriatal neurotransmission significantly contribute to heroin relapse vulnerability. In animal models, self-administration extinction produce cellular both neurons astrocytes within the nucleus accumbens (NA) core are required for cue-induced seeking. Specifically, decreased glutamate clearance reduced association of perisynaptic astrocytic processes with NAcore synapses allow release from prelimbic (PrL) cortical terminals engage synaptic structural plasticity medium spiny neurons. Normalizing astrocyte homeostasis drugs like antioxidant N-acetylcysteine (NAC) prevents Surprisingly, little is known about heroin-induced alterations or pyramidal projecting PrL cortex (PrL-NAcore). Here, we observe functional following (SA) as measured by electrophysiologically evoked plasmalemmal transporter 1 (GLT-1)-dependent current. We likewise observed increased complexity glial fibrillary acidic protein (GFAP) cytoskeletal arbor plasma membrane markers SA training cortex. Repeated treatment NAC during reversed enhanced association. PrL-NAcore neurons, apical tuft dendritic spine density enlarged head diameter male Sprague–Dawley rats. prevented decreases but not expansion. Moreover, co-registry GluA1 subunit AMPA receptors dendrite shaft heads Interestingly, accumulation immunoreactivity was further potentiated extinction. Finally, show elimination thrombospondin 2 (TSP-2) block relapse. Taken together, our data reveal circuit-level morphology potentially linked at synapses. Additionally, these demonstrate reverses SA-and-extinction-induced