The blockade of D1- and D2-like dopamine receptors within the dentate gyrus attenuates food deprivation stress-induced reinstatement of morphine-extinguished conditioned place preference in rats

Abstract

The high rate of relapse to drug abuse is one of the main problems in the treatment of addiction. Stress plays an essential role in relapsing to drug abuse. The present study investigates the role of D1- and D2-like dopamine receptors in the dentate gyrus (DG) of the hippocampus on the reinstatement of morphine (5 mg/kg)-induced conditioned place preference (CPP) both by food deprivation stress (FDS) and a sub-threshold dose of morphine (0.5 mg/kg, s.c.). All the animals in this study experienced pre-test, conditioning, post-test (expression), extinction, and reinstatement phases. The CPP scores of the pre-test and post-test were compared between the groups, and a significant difference between the CPP scores of the pre- and post-test was the criterion for the induction of CPP. Extinction continued for each animal until the calculated score for two consecutive days became the same as the pre-test score. The animals received different doses of SCH-23390 or Sulpiride (0.25, 1 and 4 μg/0.5 μl vehicle), as D1- and D2-like dopamine receptor antagonists, into the DG. After the administration of the antagonists, the animals were deprived of food for 24 h. Then, on the reinstatement day, they received a sub-threshold dose of morphine and afterwards, the conditioning scores were measured. The results demonstrated that the effective doses 50% of SCH-23390 and Sulpiride on the reinstatement induced by FDS and morphine was 1.37 and 2.28 (μg/0.5 μl vehicle per side), respectively. The results also showed that both antagonists can lead to a decrease in morphine reinstatement, and this effect was in a dose-dependent manner. In conclusion, these results indicate that D1- and D2-like dopamine receptors in the DG may be a potential target for preventing relapse to drugs in stressful life conditions.