Increase in Citrate and KCl Consumption during Morphine Withdrawal Period is Associated with Reduced Levels of Zinc and Brain-derived Neurotrophic Factor, and Poor Neurogenesis in Male Isolated Rats

Abstract

Introduction: Sustained remission from substance abuse is often difficult to achieve. However, there are certain factors that may predict the remission from substance dependence during drug withdrawal period. The aim of this study was to assess the possible predictors and patterns associated with drug abuse remission. Methods and Materials: Fifty-four male Sprague-Dawley rats were divided into four groups 1) socialized group 2) isolated group 3) withdrawal-socialized group 4) withdrawal-isolated group. Rats first received morphine for 7 days and then, were withdrawn from it. BrdU (5-bromo-2’- deoxyuridine) was injected from day 1 to day 14 of the experiment. At the end of the experiment, BDNF, MDA and zinc levels were assessed. We used Open-Field Test (OFT) to study drug sensitization and anxiety levels. Furthermore, citrate and KCl consumption, mood state, and neurogenesis were also evaluated. Results: Zinc and BDNF levels were markedly higher is withdrawal-socialized group. Furthermore, withdrawal-isolated group consumed more citrate and KCl and demonstrated more drug sensitization than the withdrawal-socialized group. In addition, anxiety, MDA, and corticosterone levels were significantly elevated in withdrawal-isolated rats. Both socialized groups had more BrdU-positive cells as compared to isolated groups. Conclusion: Socialization during the withdrawal period may facilitate remission from drug abuse and improve neurogenesis.