The role of NMDA glutamate receptors in the lateral habenula on morphine‐induced conditioned place preference in rats

Abstract The lateral habenula (LHb) has received special attention due to its role in modulating motivated behavior, stress response, and rewarding and aversive stimuli through monoamine transmission. In the present study, the involvement of the N ‐methyl‐ d ‐aspartate (NMDA) receptors of the LHb in the expression and acquisition phases of morphine‐induced conditioned place preference (CPP) was studied in male rats. Bilateral injections of agonist/antagonist (MK‐801) of NMDA receptor were performed during the conditioning sessions of the acquisition phase. In other separate groups, drugs were also injected into the LHb before the test session during the expression phase of CPP. A 5‐day CPP bias paradigm was used to study the effect of injections of NMDA and MK‐801 into the LHb on morphine reward‐related behavior. Different doses of NMDA plus morphine reduced the CPP score during the acquisition phase, whereas MK‐801 significantly increased conditioning scores during the acquisition phase of CPP. The injection of agonists and antagonists of NMDA receptors in LHb had no significant effect on CPP scores and locomotion during the expression phase of CPP, whereas the motor activity in the acquisition phase was affected by the drugs. The reduction effect of NMDA on the CPP scores during the acquisition phase was blocked by pretreatment with MK‐801. Our findings also suggest that NMDA receptors in the LHb may be involved in the acquisition phase of morphine‐induced CPP.