Solmaz Fallahi - MSC of physiology, Department of physiology, School of Medical faculty, Tabriz University of Medical Sciences, Tabriz, Iran.
Gisou Mohaddes - PHD. of physiology, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Hamid Soltani Zangbar - PHD. of Neuroscience, Department of Neuroscience, School of Advanced Medical sciences, Tabriz University of Medical Sciences, Tabriz, Iran

Background and Aim : Methamphetamine affects the central nervous system (CNS) by impairing cognitive function and inducing apoptosis. The cognitive enhancing and hippocampal neuroprotective effects of ghrelin have been shown previously. This study aimed to investigate the effects of ghrelin on cognitive function and apoptosis pathway in methamphetamine-received male rats. Methods : Sixty adult male Wistar rats were used in this study which were randomly divided into six groups (n=10): Saline/Saline (S-S), Saline/Ghrelin (S-G), Methamphetamine/Simultaneous Saline (M-SS), Methamphetamine/Simultaneous Ghrelin (M-SG), Methamphetamine/Delayed Saline (M-DS), and Methamphetamine/Delayed ghrelin (M-DG). Methamphetamine (5 mg/kg) and ghrelin (5 nm/kg) were injected intraperitoneally. Spatial and passive avoidance memories were evaluated by Morris water maze (MWM) and Shuttle box, respectively. Hippocampal expression levels of Cytochrome-C, Caspase 3, and Bax/Bcl-2 ratio were evaluated by Western blotting. TUNEL study was performed to detect neuronal apoptosis of the hippocampusResults : Our results showed that time spent in the target quadrant in M-SS group was significantly (p<0.05) less than control group. Whereas, delayed ghrelin treatment could significantly (p<0.05) increase it. None of the initial latency (IL) and step through latency (STL) parameters of passive avoidance test was significant between groups. Moreover, methamphetamine significantly (p<0.001) increased hippocampal protein expression of Caspase 3 and Cytochrome-C, and BAX/Bcl-2 ratio, which was significantly (p<0.001) decreased by ghrelin treatment. TUNEL assay showed a significant (p<0.001) increase in the number of apoptotic cells in methamphetamine-received animals, while ghrelin treatment significantly (p<0.001) decreased apoptosis. Conclusion : These results indicate that ghrelin treatment could improve spatial memory and reduce neuronal apoptosis in the hippocampus of methamphetamine-received animals

Methamphetamine; Ghrelin; Memory; Apoptosis; Hippocampus