Effects of Limonene on Chronic Restraint Stress-Induced Memory Impairment and Anxiety in Male Rats

Limonene is a natural monoterpene having antioxidant, anti-inflammatory, and neuro-protective properties. We investigated the effects of limonene on memory impairment, hippocampal damage, and high anxiety induced by chronic immobilization stress in male rats. Fourty male Wistar rats were divided into the control (C), limonene (L), stress (S), and stress+limonene (S+L) groups. Animals of the S and S+L groups were put in a restrainer daily for 6 h for 21 consecutive days. Within the same period, the L and S+L groups were treated with limonene (10 mg/kg, gavaging). The Morris water maze (MWM) and elevated plus-maze (EPM) tests were used to evaluate spatial learning, formation of memory, and the anxiety level. At the end of the course, structural hippocampal damage was evaluated by Nissl's staining. Chronic immobilization reduced memory, caused the emergence of anxiety, and induced neuronal loss in the CA1 area of the hippocampus. The duration and distance traveled to reach the hidden platform in the MWM test in the S+L group were significantly smaller compared with those in the S group (P < 0.05), while time spent in the target quadrant was significantly greater compared with the latter group (P < 0.01). Also, limonene provided a significant increase in the percentage of open-arm entries and stay in these arms of the EPM, as compared with the S group (respectively, P < 0.01 and P < 0.05), and reduced stress-induced damage in CA1 pyramidal neurons in these animals. It is concluded that limonene provides spatial memory improvement and reduces anxiety in rats exposed to immobilization stress; it may appear efficient in treating neurodegenerative diseases.