Low Current Intensity Plus an Ineffective Dose of Morphine Affect Conditioning Place Preference Through Different Pathways in the Lateral Habenula.

Abstract

Background: The involvement of lateral habenula and the ineffective dose of morphine on reward-related learning and memory is less well-known. This study looked into the effects of electrical stimulation, GABA_B receptor blockade, and a combination of both with morphine on conditioned place preference.

Materials and methods: In this experiment, male rats were anesthetized with ketamine/xylazine (six rats in each group). A 5-day biased conditioned place preference paradigm was used for the behavioral test. The effects of electrical stimulation and phaclofen plus a low dose of morphine on the acquisition and expression phases were examined during conditioning sessions and before the test phase, respectively.

Results: The conditioning scores were reduced by antagonist injection during the acquisition phase. Interestingly, different intensities exhibited opposite effects on the acquisition phase. Conditioned place preference scores during the acquisition phase were significantly induced by 25 μA electrical stimulation, while conditioning scores were suppressed by electrical stimulation at 150 μA. Phaclofen (2 μg/rat) combined with high intensity induced aversion during the acquisition phase, while inhibiting expression. In contrast, high intensity with phaclofen (1 μg/rat) inhibited only the acquisition session. However, low intensity during the acquisition phase had an additive effect that was prevented by pretreatment with phaclofen (2 μg/rat), but this response was modified by the antagonist's low dose.

Conclusions: A behavioral technique called conditioned place preference is frequently used to evaluate learning that is related to rewards. Therefore, lateral habenula electrical stimulation and phaclofen plus morphine could affect place preference through the involvement of the reward system.