Involvement of the ERK signaling pathways in the NAc in propofol-seeking behavior induced by cues in rats

Propofol, an intravenous short-acting anesthetic, has the potential to induce craving and relapse. Accumulated evidence demonstrates that extracellular signal-regulated kinase (ERK) plays an essential role in drug reward and relapse. In the previous study, we demonstrated that the ERK signaling pathways in the Nucleus accumbens (NAc) were involved in propofol reward. However, the role of the ERK signaling pathways in propofol relapse is still unknown. We first trained rats to self-administer propofol for 14 days, then evaluated propofol-seeking behavior of relapse induced by a contextual cues and conditioned cues after 14-day withdrawal. Meanwhile, MEK inhibitor U0126 was used to investigate the role of the ERK signal pathways in propofol-seeking behavior induced by contextual cues and conditioned cues. Results showed that the number of active nose-poke responses in propofol-seeking behavior induced by conditioned cues was much higher compared to contextual cues. U0126 (5.0 μg/side, Lateral Ventricle (LV)) pretreatment significantly decreased the active responses induced by conditioned cues, which was associated with a large decline in the expression of p-ERK in the NAc. Moreover, microinjectionofU0126 (2.0 μg/side) in the NAc also attenuated the active responses of propofol-seeking behavior. Additionally, microinjections with U0126 in the LV (5.0 μg/side) or NAc (2.0 μg/side) both failed to alter sucrose self-administration or locomotor activity of rats. Therefore, we conclude that ERK phosphorylation in the NAc maybe involved in propofol relapse.