RESUMEN
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 (200-220â¯g) were allocated into 7 groups, including 5 groups of saline, METH (1, 2â¯mg/kg), Agmatine (5, 10â¯mg/kg) and 2 groups of agmatine (5, 10â¯mg/kg) with higher doses of METH (2â¯mg/kg) for 5 consecutive days (nâ¯=â¯8 in each group). All injections were done intraperitoneally and agmatine was administrated 10â¯min before METH treatment. Furthermore, Passive avoidance learning (PAL) test was assessed on the 5th day. Retention test was done 24â¯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 (10â¯mg/kg) significantly decreased impairment effect of METH (2â¯mg/kg) on PAL and memory. Also, molecular results revealed that METH (2â¯mg/kg) markedly decreased hippocampal CaMKII-α gene expression while agmatine (10â¯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.