Ethanol induces long-term facilitation of NR2B-NMDA receptor activity in the dorsal striatum: implications for alcohol drinking behavior - PubMed (original) (raw)

LTF of NMDAR EPSCs in the rat dorsal but not ventral striatum. A, Ethanol-mediated induction of LTF in the dorsal striatum. Left, Time course of NMDAR EPSCs recorded before, during (15 min as indicated by the horizontal bar), and after 50 and 100 m

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ethanol application. Note that the mean EPSC amplitude is facilitated after ethanol washout (n = 15 slices). The inset shows sample traces at times 1, 2, and 3. The stimulus artifacts have been omitted for clarity. Calibration: 100 ms, 100 pA. Middle, Same as left, but with 50 m

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ethanol. Right, Bar graph comparing the direct (EtOH) and washout (post-EtOH) effects of different concentrations of ethanol on NMDAR EPSCs. EPSCs were averaged from 10–14 min after ethanol application (EtOH), and from 21–30 min after ethanol washout (post-EtOH). #p < 0.01, *p < 0.05 versus baseline (average of EPSCs over the 10 min before ethanol application) by paired Student's t test; ##p < 0.05. B, Ethanol failed to induce LTF in the ventral striatum. Left, Time course of NMDAR EPSCs recorded in the ventral striatum before, during, and after 100 m

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ethanol application. Note that, on average, no LTF was observed (n = 14 slices). Right, Bar graph comparing the ethanol (100 m

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) effect on mean NMDAR EPSCs in the dorsal (same data as A, left) and the ventral (same data as B, left) striatum. #p < 0.01, *p < 0.05 versus baseline; **p < 0.05. C, Sustained NR2B subunit phosphorylation after ethanol washout in the dorsal striatum. Dorsal or ventral striatal slices were treated with 100 m

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ethanol for 20 min. The slices were homogenized and the NR2B subunit was immunoprecipitated. Phosphorylation of the NR2B subunit was detected by anti-[pY1252]NR2B antibodies (pY; top). The membrane was stripped and reprobed with anti-NR2B antibodies (bottom). The image is representative of three independent experiments. Quantification of the level of pYNR2B (p-NR2B) to total immunoprecipitated NR2B subunits is shown. *p < 0.05, **p < 0.01 versus control; n = 3 experiments, two rats per experiment. D, Sustained activation of Fyn activity after ethanol washout in the dorsal striatum. Dorsal or ventral striatal slices were treated with 100 m

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ethanol for 15 min. Ethanol was removed, and fresh aCSF was added for 10 min. The slices were homogenized, and Fyn was immunoprecipitated with anti-Fyn antibodies. Activation of Fyn was detected by anti-[pY417]Fyn antibodies (pY; top). The blot was stripped and reprobed with anti-Fyn antibodies (bottom). The image is representative of four independent experiments. Quantification of the level of [pY417]Fyn (p-Fyn) to total immunoprecipitated Fyn is shown. *p < 0.05, **p < 0.01 versus control; n = 4 experiments, two rats per experiment.