Lanthanum and zinc sensitivity of GABA_A-activated currents in adult medial septum/diagonal band neurons from ethanol dependent rats

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• 作者：Frye ; Gerald D. ; Fincher ; Annette S. ; Grover ; Cathy A. ; Jayaprabhu ; Sudheer
• 关键词：Ethanol ; Physical dependence ; GABA_A receptor ; Desensitization ; Lanthanum ; Zinc ; Dissociated neuron ; Septum
• 刊名：Brain Research
• 出版年：1996
• 出版时间：May 13, 1996
• 年：1996
• 卷：720
• 期：1-2
• 页码：101-110
• 全文大小：1.01 M

文摘

The impact of chronic ethanol treatment, sufficient to induce tolerance and physical dependence, on GABA_A receptor function was studied in acutely isolated neurons from the medial septum/nucleus diagonal band (MS/nDB) of adult rats using whole cell, patch-clamp recordings. In ethanol-naive Controls, GABA (0.3-300 μM) induced concentration-dependent increases in Cl⁻ current with a threshold of 0.3-1 μM, a mean maximal current of 7645 ± 2148 pA at 100-300 μM, an EC₅₀ of 11.3 ± 1.3 μM and a slope of 1.53 ± 0.07. GABA-activated currents in neurons from animals receiving two weeks of ethanol liquid diet treatment did not differ significantly on any of these measures. The rate of GABA_A receptor desensitization (t = 6.49 ± 1.19 s) estimated as the time required for loss of 50 % of peak current during sustained application of 10 μM GABA, as well as the residual steady state current remaining following complete desensitization for controls was unchanged by chronic ethanol. The impact of chronic ethanol treatment on the GABA_A receptor modulation by lanthanum and zinc which act as positive and negative allosteric modulators, respectively, was also evaluated. Test pulses of 3 μM GABA in control neurons showed maximal potentiation by 141 ± 30 % at 1000 μM lanthanum with an EC₅₀ of 107 ± 34 μM and a slope of 1. Lanthanum potentiation remained the same following chronic ethanol treatment. Initial estimates based on fitted concentration response curves suggested that maximal inhibition of 3 μM GABA responses by zinc at the level of 70.2 ± 8.5 % in control cells was significantly increased by chronic ethanol treatment to 95.3 ± 2.5 % , although the IC₅₀ of 60.2 ± 25 μM was not changed. However, this difference was not supported by direct tests of maximal 3-10 mM zinc concentrations. These results suggest that chronic ethanol treatment, sufficient to induce tolerance and physical dependence, probably does not lead to readily detectible changes in GABA_A receptor function in MS/nDB neurons.