It has been shown that morphine addiction impairs cognitive brain functions. However, there is no document to consider the effect of morphine dependency and its withdrawal on cost-benefit decision making and its molecular pathways. The present study aimed to evaluate the influences of morphine dependency and its withdrawal on delay-based decision making and the BDNF, p-GSK3β, and p-CREB levels during the decision making in the hippocampus. Different groups of rats were trained in a T-maze with the delay-based cost-benefit decision-making paradigm. After that, the animals were dependent on morphine, and the percentage of the high reward preference was evaluated. After behavioral tests, BDNF level, p-GSK3β/GSK3β ratio, and p-CREB/CREB ratio in the hippocampus measured by Western blot analysis. The gathered data showed that level of BDNF enhanced while p-GSK3β/GSK3β ratio and p-CREB/CREB ratio in the hippocampus did not change during delay-based decision making. In morphine-dependent rats, the p-GSK3β/GSK3β ratio increased, the BDNF level and p-CREB/CREB ratio did not change in the decision making procedure. After withdrawal from morphine, the BDNF level raised while p-GSK3β/GSK3β ratio and p-CREB/CREB ratio did not change compared to the addiction group. The data declared that BDNF in the hippocampus has a critical role in delay-based decision making. Change in p-CREB in the hippocampus is not related to decision making in normal and morphine-dependent rats. P-GSK3 in the hippocampus is not involved in the decision making in normal rats, but during decision making in morphine-dependent rats, its level increased.