PM284. Agmatine prevents learning and memory deficit in repeated morphine withdrawal: Is it via glutamatergic system?

Objectives: Opioid addiction is associated with long-term adaptive changes in the brain that involve glial activation. Agmatine is an amine formed by the decarboxylation of l-arginine by the enzyme arginine decarboxylase. It binds to α2-adrenergic and imidazoline receptors, and selectively blocks N-methyl-Daspartate receptors. Agmatine treatment was reported to have various biological actions. It reduces tolerance to morphine and attenuates behavioral signs of morphine in naloxoneinduced abstinence syndrome in vitro and in. This study has been designed to evaluate the effect of agmatine on morphineinduced glial activation in rats. Methods: Male Wistar Albino rats (190–240 g) were divided into three groups such as Control, Morphine and Morphine+Agmatine. Morphine and Morphine+Agmatine groups were received two morphine pellets containing 75 mg morphine base each that was implanted subcutaneously in the scapular area under light anesthesia. Morphine+Agmatine group received agmatine (40 mg/kg, i.p.) and the injection was repeated after 6 hours. 72 hours later naloxone 2 mg/kg i.p was injected to precipitate withdrawal syndrome, observed for 30 minutes and withdrawal symptoms were recorded. Control group received placebo pellets and only saline injections in the same volume of agmatine. Immunohistochemistry was performed to investigate the expression of glial fibrillary acidic protein (GFAP) as indicator of glial activity and c-fos. Results: Morphine withdrawal syndrome became more severe as it is repeated. When coadministered with morphine, agmatine significantly attenuated withdrawal symptoms. Immunohistochemistry with GFAP revealed that agmatine significantly decreased morphine-induced over-expression of GFAP and c-fos. Conclusions: Exogenously applied agmatine can prevent morphine-withdrawal-induced glial reactivity and c-fos. As an endogenous molecule agmatine might be a part of compensatory mechanism within the reward pathway. Therefore further studies are required for better understanding the involving mechanisms in order to develop novel approaches for the morphine addiction strategies. PM284 Agmatine prevents learning and memory deficit in repeated morphine withdrawal: Is it via glutamatergic system? Feyza Aricioglu1, Aydın Sav2 1Marmara University, Faculty of Pharmacy, Department of Pharmacology and Psychopharmacology Research Unit, Istanbul 2Marmara University, Faculty of Medicine, Department of Pathology,