Protection against Morphine-Induced Inhibitory Avoidance Memory Impairment in Rat by Curcumin: Possible Role of Nitric Oxide/ cAMP-Response Element Binding Protein Pathway

Abstract

Background: Although a substantial body of research suggests curcumin (CUR) has the preventive potential in memory impairment, the mechanism by which CUR prevents memory loss is still being investigated. This study employs an inhibitory avoidance (IA) model to investigate whether CUR can prevent morphine (Mor)-induced memory impairment as well as the possible role of cAMP-response element binding (CREB) protein, and nitric oxide (NO) signaling in this mechanism. Methods: This experimental study was conducted at the Animal Lab of the Physiology Research Center, Kashan University of Medical Sciences (Kashan, Iran) in 2018. Forty rats were randomly divided into four groups: control, CUR (pretreatment gavage of CUR [10 mg/Kg] for 35 days), Mor (7.5 mg/Kg, i.p.), and CUR+Mor (n=10 per group). Following the evaluation of the IA memory and locomotor activity of the animals, the CREB protein expression in the hippocampus and NO metabolites (NOx) level in the brain tissue were also investigated. The data were analyzed using Sigmaplot software (version 14.0) by using the ANOVA, Kruskal–Wallis, Holm-Sidak, and Dunn’s post hoc tests. P<0.05 was considered to be statistically significant. Results: In the Mor group, the IA memory of the rats was significantly impaired (P=0.001). CUR prevented the Mor-induced IA memory impairment (P=0.075). While the Mor treatment decreased the phosphorylated CREB (p-CREB) expression, the CUR+Mor cotreatment increased p-CREB expression (P=0.010). Nevertheless, the Mor treatment increased the total CREB expression (P=0.010). The NOx concentration in the brain tissue was decreased following the Mor treatment (P=0.500) but increased after the CUR+Mor cotreatment (P=0.001). Conclusion: The present findings suggest that CUR prevents the memory impairment of rats, possibly through NO and its downstream CREB signaling.

Keywords

• memory
• morphine
• curcuma
• nitric oxide
• creb-binding protein