INVESTIGATION OF PREFRONTAL CORTICAL CELL FIRING DURING REINSTATEMENT OF METHAMPHETAMINE-SEEKING IN RAT: ROLE OF GLUCOCORTICOID RECEPTORS IN THE BASOLATERAL AMYGDALA FOLLOWING ACUTE AND CHRONIC RESTRAINT STRESS

Background and Aim : Methamphetamine (METH) is a neurotoxic psychostimulant with highly addictive potential and leads to compulsive drug use and vulnerability to relapse. Considering the important role of stress and the prefrontal cortex in the reinstatement process, in this study, we tried to find out the investigation of prefrontal cortical cell firing during reinstatement of methamphetamine-seeking in rat: Role of glucocorticoid receptors in the basolateral amygdala following acute and chronic restraint stress. Methods : Administration of METH (0.125, 0.25, 0.5, 1, 2 and 4 mg/kg) could induce CPP. In extinction phase, rats were put in the CPP box for 30 min per day for 8 consecutive days. After extinction, animals were exposed to restraint stress (3-h period, as an acute stress) before subcutaneous administration of ineffective dose of METH (0.125 mg/kg) in order to reinstate the extinguished METH-induced CPP. For induction the chronic stress during extinction phase animal exposed the restraint stress for a 1-h period/day. In the second phase animals unilaterally received GRs antagonist (3, 10, 30 and 90 ng/0.3 µl DMSO). The electrophysiology section was conducted following the extinction phase. Firing activity was recorded for 50 min during the reinstatement phase. Results : The results showed that the effective dose of METH to induce CPP was 0.5 mg/kg and acute and chronic restraint stress can significantly induce reinstatement of METH-induced CPP (P˂0.001) in extinguished animals. Additionally, the chronic restraint stress could reduce duration of extinction. Also, intra-BLA GRs antagonist prevented the stress-induced reinstatement. Also, threshold dose, but not the sub-threshold dose, of METH significantly increased PFC neural activity in the control animals. The sub-threshold dose of METH notably changed this activity in groups that received stress. Conclusion : It can be proposed that stress partially exerts its effect on the reward pathway via GRs in the BLA, Also, 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.

کلیدواژه ها:

Restraint stress ، Methamphetamine ، Glucocorticoid receptor ، Basolateral amygdala ، Prefrontal cortex ، Neuronal activity