Effect of acute and chronic restraint stress on electrical activity of prefrontal cortex neurons in the reinstatement of extinguished methamphetamine-induced conditioned place preference: An electrophysiological study

Abstract Increased vulnerability to drug abuse has been observed after exposure to stress and the prefrontal cortex (PFC) plays a major role in the control of the stress response and reward pathway. The current study was conducted to clarify the effects of acute and chronic restraint stress on PFC neural activity during the reinstatement of methamphetamine (METH)-induced conditioned place preference (CPP) in rats. Following the establishment of CPP (METH 0.5 mg/kg; s.c. for 3 days) and the extinction phase, male Wistar rats were divided into threshold (0.25 mg/kg; s.c.) and sub-threshold (0.125 mg/kg; s.c.) METH-treated super groups to induce reinstatement. Each super group contained control (non-stressed), acute restraint stress (ARS) and chronic restraint stress (CRS) groups. in vivo single unit recordings were performed on the urethane-anesthetized rats in these groups. After baseline recordings (10-min period) of the neurons in the PFC, their firing activity was recorded for 50 min during the reinstatement phase after injection of METH. The results showed that the threshold dose, but not the sub-threshold dose, of METH significantly increased PFC neural activity in the non-stressed animals. The sub-threshold dose of METH notably changed this activity in both the ARS and CRS groups. These changes in the excited neurons after the sub-threshold dose in the ARS and CRS groups were significantly higher than those in the non-stressed group. It appears that the PFC is implicated in the associated reward pathway and stress functions. METH affected the firing rate of PFC neurons and stress amplified the effect of METH on changes in the neuronal firing rate in the PFC.