Neuroprotective effect of ghrelin in methamphetamine-treated male rats.

This study aimed to investigate the effects of ghrelin, as a neuroprotective agent, on cognitive impairment and apoptosis pathway in methamphetamine-treated male rats. Sixty adult male Wistar rats were randomly divided into six groups (n = 10): Saline/Saline (SS), Saline/Ghrelin (SG), Methamphetamine/Simultaneous Saline (MSS), Methamphetamine/Simultaneous Ghrelin (MSG), Methamphetamine/Delayed Saline (MDS), and Methamphetamine/Delayed ghrelin (MDG). 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 assay was performed to detect hippocampal neuronal apoptosis. Our results showed that time spent in the target quadrant in MSS group was less than the control group. However, simultaneous ghrelin treatment could increase it. Ghrelin treatment reversed methamphetamine effects on hippocampal protein expression of Caspase 3 and Cytochrome-C, and BAX/Bcl-2 ratio. TUNEL assay showed an increase in the number of apoptotic cells in methamphetamine-treated animals, while ghrelin treatment decreased apoptosis. These results indicate that ghrelin treatment could improve spatial memory and reduce neuronal apoptosis in the hippocampus of methamphetamine-treated animals.