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Agmatine attenuates methamphetamine-induced passive avoidance learning and memory and CaMKII-α gene expression deteriorations in hippocampus of rat
- Noorbakhshnia, Maryam, Rashidkaboli, Arsham, Pakatchian, Mahnaz, Beheshti, Siamak
- Physiology & behavior 2018 v.194 pp. 491-496
- agmatine, cognition, gene expression, genes, hippocampus, males, memory, memory disorders, methamphetamines, polyamines, quantitative polymerase chain reaction, rats, storage temperature, therapeutics
- Methamphetamine (METH) abuse is one the most worldwide problems with wide-ranging effects on the central nervous system (CNS). Chronic METH abuse can associate with cognitive abnormalities and neurodegenerative changes in the brain. Agmatine, a cationic polyamine, has been proposed as a neuromodulator that modulates many effects of abused drugs. The aim of this study was to determine if agmatine can decrease the impairment effect of METH on memory and hippocampal CaMKII-α gene expression, a gene that plays a major role in memory. Male wistar rats (200–220 g) were allocated into 7 groups, including 5 groups of saline, METH (1, 2 mg/kg), Agmatine (5, 10 mg/kg) and 2 groups of agmatine (5, 10 mg/kg) with higher doses of METH (2 mg/kg) for 5 consecutive days (n = 8 in each group). All injections were done intraperitoneally and agmatine was administrated 10 min before METH treatment. Furthermore, Passive avoidance learning (PAL) test was assessed on the 5th day. Retention test was done 24 h after training and the rats were sacrificed immediately. Hippocampi were removed and stored at −80 °C. Finally, hippocampal CaMKII-α gene expression was measured using Quantitative Real-time PCR. Our data showed that chronic METH dose-dependently impaired PAL retrieval, as it decreased step-through latency (STL) and increased time spent in the dark compartment (TDC). While Agmatine with a higher dose (10 mg/kg) significantly decreased impairment effect of METH (2 mg/kg) on PAL and memory. Also, molecular results revealed that METH (2 mg/kg) markedly decreased hippocampal CaMKII-α gene expression while agmatine (10 mg/kg) co-adminstration prevented it. Taken together, the results propose that agmatine may provide a potential therapy for learning and memory deficits induced by METH.