Slawecki C J, Purdy R H, Li T K, Walpole T, Ehlers C L
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Alcohol Clin Exp Res. 2000 Sep;24(9):1369-75.
Alcohol preferring (P) and alcohol-nonpreferring (NP) rats have been shown to have differing behavioral and electrophysiological responses to drugs that are positive modulators of the gamma-aminobutyric acid type A (GABA-A) receptor complex, such as ethanol and benzodiazepines. The neuroactive steroid allopregnanolone is also a positive modulator of GABA-A receptors; therefore, we hypothesized that P and NP rats would respond differently to intraperitoneally administered allopregnanolone.
Male P and NP rats were implanted with screw electrodes that overlay the frontal and parietal cortices and with a depth electrode aimed at the amygdala. Allopregnanolone (0.0-10.0 mg/kg ip) was administered 10 min before recording the EEG.
Allopregnanolone increased high-frequency power (8-32 Hz) in the cortex and amygdala of both P rats and NP rats. In addition, allopregnanolone increased the predominant frequency of the cortical EEG in the 8 to 16 Hz bandwidth, decreased the predominant frequency in the 32 to 50 Hz bandwidth, and increased EEG variability (16-50 Hz). The effects of allopregnanolone were qualitatively similar in P and NP rats. However, P rats were more sensitive to low doses of allopregnanolone in cortex, whereas NP rats responded to lower doses of allopregnanolone in the amygdala.
These data indicate that P and NP rats differ in their sensitivity to the EEG effects of allopregnanolone in the cortex and amygdala, which suggests that differences in GABAergic systems between P and NP rats may contribute to some of the differences observed in their behavioral repertoire.
酒精偏好（P）大鼠和酒精非偏好（NP）大鼠对作为γ-氨基丁酸A型（GABA-A）受体复合物正向调节剂的药物，如乙醇和苯二氮䓬类药物，表现出不同的行为和电生理反应。神经活性甾体别孕烯醇酮也是GABA-A受体的正向调节剂；因此，我们推测P大鼠和NP大鼠对腹腔注射别孕烯醇酮的反应会有所不同。
雄性P大鼠和NP大鼠植入覆盖额叶和顶叶皮质的螺旋电极以及一根指向杏仁核的深度电极。在记录脑电图前10分钟给予别孕烯醇酮（0.0 - 10.0毫克/千克，腹腔注射）。
别孕烯醇酮增加了P大鼠和NP大鼠皮质及杏仁核的高频功率（8 - 32赫兹）。此外，别孕烯醇酮增加了8至16赫兹带宽内皮质脑电图的主导频率，降低了32至50赫兹带宽内的主导频率，并增加了脑电图变异性（16 - 50赫兹）。别孕烯醇酮对P大鼠和NP大鼠的影响在性质上相似。然而，P大鼠对皮质中低剂量的别孕烯醇酮更敏感，而NP大鼠对杏仁核中较低剂量的别孕烯醇酮有反应。
这些数据表明，P大鼠和NP大鼠对别孕烯醇酮在皮质和杏仁核中脑电图效应的敏感性不同，这表明P大鼠和NP大鼠之间GABA能系统的差异可能导致了它们在行为表现中观察到的一些差异。
