Brain research
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Astroglial cells clear extracellular glutamate through the glutamate transporters, GLT-1 and GLAST, and subsequently convert the incorporated glutamate into glutamine by the enzyme, glutamine synthetase (GS). Several forms of acute brain injury are associated with the increased expression of GS and the decreased expression of GLT-1 and/or GLAST, eventually leading to the accumulation of excitotoxic extracellular glutamate concentrations. Although of clinical interest, the actual trigger of these injury-related changes of glial glutamate turnover remains unknown. ⋯ Glutamate at >or=1 mM induced a prolonged increase of GS expression in contrast to glutamate transporters. Neither the decline of glutamate transporter expression nor the increase in GS expression induced by high extracellular glutamate was further modulated by mild hypoxia. Whereas the stimulatory influences of glutamate on GS expression were prevented by the non-competitive NMDA receptor antagonist, MK801, the inhibitory influences on glutamate transporter expression were neither sensitive to MK801, the non-competitive mGluR5 antagonist, MTEP, nor the non-competitive AMPA receptor antagonist, GYKI52466, implying that glutamate controls glial glutamate transport by a glutamate receptor-independent mechanism.
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The effects of chronic morphine exposure on synaptic plasticity in the CA1 region of the hippocampal slice preparation using extracellular recordings of the population spike (PS) evoked in response to Schaffer collateral stimulation were studied. High frequency stimulation (HFS; 1X100 Hz) and theta pulse stimulation (TPS; 5 Hz trains for 3 min) were used as patterned activities. The results showed that in rats chronically treated with morphine (dependent group), TPS induced long-term depression (LTD) of PS in CA1 in the absence of in vitro morphine. ⋯ It is concluded that morphine withdrawal was associated with greater depression of CA1 PS elicited by natural stimulus induced activity pattern. This effect was associated with changes in NMDA and adenosine receptors due to chronic morphine administration. Such an in vitro preparation could provide a novel paradigm to investigate withdrawal effects on synaptic plasticity.