Neural dynamics of addiction memory retrieval: prelimbic-VTA local field potential power and coherence during morphine seeking reinstatement.

Relapse to opioid use, driven by the retrieval of powerful drug-associated memories, remains a major clinical obstacle. The neurophysiological mechanisms within the prelimbic cortex (PrL)-ventral tegmental area (VTA) circuit that govern this reinstatement of drug-seeking are poorly defined. This study aimed to identify the specific electrophysiological signatures of morphine-primed reinstatement by analyzing local field potential (LFP) activity and PrL-VTA coherence in a rat model of conditioned place preference (CPP). Following conditioning, morphine-treated rats exhibited decreased beta power in the PrL, while the VTA showed a broad increase in power across theta, alpha, beta, and gamma frequencies. These oscillatory changes largely persisted after extinction. The findings reveal distinct neural state during relapse. Morphine-primed reinstatement was uniquely marked by a specific reduction in VTA beta power. Furthermore, the PrL showed opposing changes in low- and high-frequency bands, characterized by increased delta and theta power alongside decreased high-gamma power. Most notably, a widespread alteration in the PrL-VTA circuit emerged, involving higher delta, alpha, and high-gamma coherence, but lower theta and low-gamma coherence. These results suggest that the retrieval of opioid-associated memories is not simply a return to a pre-extinction state but is governed by a distinct neurophysiological pattern. Specifically, the reorganization of information flow between the PrL and VTA emerges as a critical biomarker for the reinstatement of addiction memory. These signatures offer new insights into the circuit-level dynamics of relapse and may help inform the development of future therapeutic interventions.