Attenuation of morphine conditioned place preference and reinstatement by vitamin D

Abstract

Opioid action in the brain involves the dopamine-reward system as well as non-dopamine pathways. Since vitamin D also modulates the brain’s dopamine system, the question of this study was how vitamin D might affect the opioid influences on the reward system. Therefore, the objective of this study was to investigate the possible effect of vitamin D on the conditioned place preference (CPP) induced by morphine, as a valuable model of assessment of the reinforcing properties of opioids by associating the context to the rewarding properties of the addictive drugs. Male Wistar rats were randomly divided into two main groups that either received saline (morphine vehicle) or morphine (5 mg/kg, intraperitoneally) for CPP. Each of the main groups was divided into three vitamin D treatment subgroups: vitamin D vehicle and vitamin D (5 and 10 μg/kg, intraperitoneally). Vitamin D injections were started 1 week ahead of the experiment (two injections) or immediately after post-conditioning and in both cases, it was continued twice weekly throughout the CPP. Administration of vitamin D (10 μg/kg) before conditioning in CPP markedly attenuated morphine expression in the post-conditioning test. Receiving vitamin D (5 or 10 μg/kg) before or after conditioning significantly attenuated morphine reinstatement. Administration of vitamin D after opioid conditioning facilitated morphine memory extinction and attenuated morphine reinstatement. Vitamin D is probably a valuable addition to be considered as a part of the treatment for prevention or minimizing the dependency or relapse to opioids.