期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 129, 期 1, 页码 87-94出版社
STOCKTON PRESS
DOI: 10.1038/sj.bjp.0703039
关键词
medial septum/diagonal band; non-NMDA glutamate receptors; AMPA receptor; ethanol intoxication; tolerance and dependence; patch-clamp electrophysiology
资金
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R01AA010067] Funding Source: NIH RePORTER
- NIAAA NIH HHS [AA10067] Funding Source: Medline
1 The direct impact of ethanol on native, non-NMDA glutamate receptors was examined in acutely isolated MS/DB neurons from rat. The impact of ethanol functional tolerance and physical dependence on non-NMDA receptor function was also determined. 2 Non-NMDA receptors were defined pharmacologically as predominantly the AMPA subtype, because both AMPA- or kainate-activated currents were blocked by GYKI 52466, a selective AMPA receptor antagonist. The relative magnitude of potentiation of AMPA-activated currents by 10 or 100 mu M cyclothiazide was consistent with recombinant AMPA flop-subtype receptors. Finally, the selective kainate receptor agonist, SYM 8021, induced little current in MS/DB neurons. 3 AMPA receptor currents when activated by kainate were sensitive to ethanol, showing inhibition of similar to 5-50% when 10-300 mM ethanol and kainate were briefly co-applied (3 s). Ethanol (100 mM) also inhibited both the initial transient peak and sustained currents activated by AMPA. Inhibition was sustained during continuous ethanol superfusions of 5 min, suggesting a lack of acute tolerance to ethanol-induced AMPA receptor blockade. 4 Rapid application of 3-3000 mu M kainate activated concentration-dependent currents in MS/DB neurons from Control and Ethanol Dependent animals that were not significantly different. Also, direct ethanol inhibition (300 mM) of kainate-activated currents was not reduced by ethanol dependence, suggesting a lack of functional tolerance. 5 These results suggest that native AMPA receptors on MS/DB neurons are inhibited by pharmacologically-relevant concentrations of ethanol. However, these receptors, unlike NMDA receptors, do not undergo adaptation with sustained ethanol exposure sufficient to induce physical dependence.
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