科研之友
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摘要
It has been proved that agmatine inhibits opioid dependence yet the neural mechanism remains unclear In the present study the effect of agmatine on the neuroadaptation of glutamate neurotransmission Induced by morphine dependence including changes of the extracellular glutamate level and glutamate receptors in the nucleus accumbens was investigated We found that agmatine (2 5-20 mg/kg s c) inhibited development of morphine dependence which was consistent with our previous report In rats repeatedly treated with morphine the glutamate level in the nucleus accumbens dialysate was markedly increased after naloxone-precipitated withdrawal When agmatine (20 mg/kg s c) was co-pretreated with morphine or was applied before naloxone precipitated withdrawal this elevation of the extracellular glutamate level was inhibited In the synaptosome model repeated morphine treatment and naloxone precipitation induced an increase in glutamate release while agmatine (20 mg/kg s c) co-pretreated with morphine reversed the increase of glutamate release However neither morphine or agmatine treatment alone nor morphine and agmatine co-administration had any influence on [3H] glutamate uptake It indicated that the elevation of the glutamate level in the nucleus accumbens might be caused by the increase of glutamate release of synaptosome in the withdrawal conditions of morphine-dependent rat Furthermore agmatine concomitant treatment with morphine entirely abolished the up-regulation of the NR1 subunit of N-methyl-D-aspartate (NMDA) receptors in the nucleus accumbens in repeated morphine-treated rats Taken together the present study demonstrated that agmatine could modulate the neuroadaptations of glutamate transmis
- 出版日期2011-1-10
