Effect of agmatine on long-term potentiation in morphine-treated rats

Agmatine is an endogenous amine derived from L-arginine that potentiates morphine analgesia and inhibits naloxone precipitated abstinent symptoms in morphine dependent rats. In this study, the effects of agmatine on long-term potentiation (LIP) in the lateral perforant path (LPP)-granule cell synapse of the rat dentate gyrus (DG) on saline or morphine-treated rats were investigated. Population spikes (PS), evoked by stimulation of the LPP, was recorded from DG region. Acute agmatine (2.5-10 mg/kg, s.c.) treatment facilitated hippocampal LTP. Acute morphine (30 mg/kg, s.c.) treatment significantly attenuated hippocampal LTP and agmatine (10 mg/kg, s.c.) restored the amplitude of PS that was attenuated by morphine. Chronic morphine treatment resulted in the enhancement of hippocampal LTP, agmatine co-administered with morphine significantly attenuated the enhancement of morphine on hippocampal LTP. Imidazoline receptor antagonist idazoxan (5 mg/kg, i.p.) reversed the effect of agmatine. These results suggest that agmatine attenuated the effect of morphine on hippocampal LIP, possibly through activation of imidazoline receptor. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.