Nerve Function. Morphine On Hippocampal Glutamate Regulation Mechanism

Although opiates have long been known to alter excitatory synaptic transmission, the evidence of its effects on neurotransmitter uptake systems is lacking. Here we showed that acute morphine treatment significantly enhances synaptosomal glutamate uptake with no observed change in protein expression, suggesting decrease of glutamate transporter activity. However, on the contrary, chronic morphine treatment caused a drastic increase of synaptosomal glutamate uptake of hippocampus in chronic morphine-treated rats, which might be produced by altering the number of functional transporters. The synaptic localization of GLTI subtype revealed by immunohistochemical analysis conflnned the effect of morphine. Moreover, long-term morphine treatment induced a robust increase of GLT1 clustered in synaptic terminals in primary culture of hippocampal neurons that was accompanied by a significant increase of glutamate uptake. These results suggest that a subtype-specific translocation of glutamate transporters contributes to long-term effects of morphine on transmitter uptake, which may represent an important neuroadaptation in opiate dependence. Accumulating evidence has indicated that there might exist some correlation between opiate reward and certain kinds of learning and memory processes. The following study attempted to investigate the correlation between individual differences in morphine reward and capacities in spatial learning and spontaneous alternation. In the present studies, good-response (GR) and poor-response (PR) mice were respectively selected according to their performance in a spatial learning test involving the Morris water maze or in a spontaneous alternation task using the Y-maze. In a place preference conditioning procedure, morphine (3.0 mg/kg) produced significant conditioned place preference (CPP) in both GR and PR mice selected by using either the Morris water maze or the Y-maze. The PR mice selected with the Morris water maze showed significantly more CPP induced by morphine than the GR mice. However, no detectable difference was observed in morphine-induced CPP between the GR and PR mice selected with the Y-maze. These results suggested that the variation in morphine- 3 induced CPP in mice is somehow differentially related to that of spatial learning but unlikely to that of spontaneous alternation. In summary, the current studies demonstrated that chronic morphine treatment altered the expression and function of glutamate transporters, and some relationship exists between learning process and morphine action. This suggested that a kind of neuroadaptation in brain structure and function could be induced by chronic morphine treatment, and might present an aberrant learning.