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 (LTP) 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 LTP, possibly through activation of imidazoline receptor.