Córdoba N E, Cuadra G R, Brioni J D, Orsingher O A
Departamento de Farmacologia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina.
J Nutr. 1992 Jul;122(7):1536-41. doi: 10.1093/jn/122.7.1536.
The anticonflict effects of ethanol, diazepam and pentobarbital were evaluated in adult rats fed a low protein diet during the perinatal period in the plus-maze test, after single injections and following chronic ethanol administration (1 g.kg-1.d-1 for 30 d). Reactivity to the anticonflict effect of these drugs was similar in control and protein-deprived rats after acute treatment. After chronic ethanol administration, control rats showed tolerance to ethanol and cross-tolerance (i.e., lower reactivity) to the anxiolytic effect of diazepam and pentobarbital. Conversely, protein-deprived rats showed greater reactivity to ethanol and lack of cross-tolerance to diazepam and pentobarbital following chronic ethanol treatment. A significantly greater density of cortical gamma-aminobutyric acid receptors subtype A (GABA-A) was detected in protein-deprived rats after chronic ethanol administration compared with the density after chronic saline treatment, whereas no differences were observed in nourished controls. This suggests that the greater anxiolytic activity detected in protein-deprived rats may correlate with higher GABA-A receptor density.
在成年大鼠的十字迷宫试验中,评估了乙醇、地西泮和戊巴比妥的抗冲突作用。这些大鼠在围产期喂食低蛋白饮食,单次注射后以及慢性给予乙醇(1 g·kg-1·d-1,持续30天)后进行评估。急性治疗后,对照大鼠和蛋白质缺乏大鼠对这些药物抗冲突作用的反应性相似。慢性给予乙醇后,对照大鼠对乙醇产生耐受性,并对地西泮和戊巴比妥的抗焦虑作用产生交叉耐受性(即反应性降低)。相反,蛋白质缺乏大鼠对乙醇表现出更高的反应性,并且在慢性乙醇治疗后对地西泮和戊巴比妥缺乏交叉耐受性。与慢性给予生理盐水后的密度相比,慢性给予乙醇后,蛋白质缺乏大鼠皮质γ-氨基丁酸A受体亚型(GABA-A)的密度显著更高,而在营养良好的对照大鼠中未观察到差异。这表明在蛋白质缺乏大鼠中检测到的更强抗焦虑活性可能与更高的GABA-A受体密度相关。