Theta-gamma coupling in the prelimbic area is associated with heroin addiction

The medial prefrontal cortex (mPFC) is implicated in the regulation of drug-seeking behavior, but the specific contributions of the mPFC prelimbic (PL) subdivision and the precise mechanisms underlying heroin abuse remain largely unclear. In the present study, we examined changes in the rhythmic ensemble activity of PL neurons after induction of heroin addiction in rats. Rats were injected daily with saline (control group) or heroin (addiction group) in the light chamber of a light-dark shuttle box, and a video tracking system was used to measure conditioned place preference (CPP) as a sign of addiction. A wireless telemetry system was used to record local field potentials (LFPs) from the PL area during expression of CPP. Before treatment, there was no difference in CPP between groups (P > 0.05). However, rats in the experimental group exhibited significant CPP (P < 0.05) in the light chamber after heroin treatment compared to before treatment and compared to control rats. During CPP, addicted rats demonstrated substantial alterations in relative θ and γ frequency band power (Ps < 0.05); moreover, the θ wave alteration was strongly coupled to γ waves in heat map analyses (P < 0.05). Collectively, these findings implicate heroin-induced alterations in PL area neural activity and θ-γ coupling in heroin addiction.