Tokunaga Sayaka, Silvers Janelle M, Matthews Douglas B
Department of Pharmacology, University of Tennessee, Memphis, Tennessee, USA.
Alcohol Clin Exp Res. 2006 Jan;30(1):1-6. doi: 10.1111/j.1530-0277.2006.00020.x.
Binge alcohol drinking among adolescents has been a serious public health problem. A model of binge alcohol, chronic intermittent ethanol exposure (CIEE), during adolescence significantly attenuates ethanol-induced spatial memory deficits in rats. However, the attenuation was absent following a 12-day ethanol-free period. Since spatial memory is hippocampal dependent, a reduction in ethanol-induced spatial memory impairments may be due to a reduction in the ability of ethanol to inhibit the firing rate of single hippocampal pyramidal neurons following CIEE.
Beginning on postnatal day 30 (P30), male adolescent Sprague-Dawley rats (Harlan) were administered 5.0 g/kg ethanol (n = 10, CIEE-treated group) or an equivolume saline (n = 10, CISE-treated group) every 48 hours for 20 days. Single hippocampal pyramidal neurons from 5 CIEE-treated rats and 5 CISE-treated rats were recorded on the day following completion of the chronic intermittent exposure procedure (animals now P50). Additionally, neurons from 5 CIEE-treated rats and 5 CISE-treated rats were recorded 12 days after the completion of the chronic intermittent exposure procedure (animals now P62).
Ethanol exposure during adolescence completely blocked ethanol-induced inhibition of hippocampal pyramidal neurons in rats that were CIEE exposed. However, the effect of CIEE on hippocampal neurophysiology was time dependent. Specifically, neurons recorded from CIEE-treated rats after a 12-day ethanol-free period had similar maximal inhibition as neurons from CISE-treated animals, although the time to reach inhibition was significantly greater in neurons from CIEE-treated rats.
Chronic ethanol exposure during adolescence produces a reduction, or tolerance, to ethanol-induced inhibition of hippocampal pyramidal neural activity. Although the tolerance was greatly reversed after a 12-day ethanol-free period, neurons from CIEE animals inhibited slower than neurons from CISE animals. Since the hippocampus is known to be involved not only in spatial memory, but also in many other types of memory formation, the altered hippocampal functions because of CIEE during adolescence should be taken as a serious warning for society.
青少年酗酒一直是一个严重的公共卫生问题。青春期的暴饮酒精模型，即慢性间歇性乙醇暴露（CIEE），可显著减轻大鼠乙醇诱导的空间记忆缺陷。然而，在12天无乙醇期后这种减轻作用消失了。由于空间记忆依赖于海马体，乙醇诱导的空间记忆损伤的减轻可能是由于CIEE后乙醇抑制单个海马锥体神经元放电率的能力降低。
从出生后第30天（P30）开始，对雄性青春期斯普拉格-道利大鼠（Harlan）每48小时给予5.0 g/kg乙醇（n = 10，CIEE处理组）或等体积生理盐水（n = 10，CISE处理组），持续20天。在慢性间歇性暴露程序完成后的第二天（动物此时为P50），记录5只CIEE处理大鼠和5只CISE处理大鼠的单个海马锥体神经元。此外，在慢性间歇性暴露程序完成12天后（动物此时为P62），记录5只CIEE处理大鼠和5只CISE处理大鼠的神经元。
青春期乙醇暴露完全阻断了CIEE暴露大鼠中乙醇诱导的海马锥体神经元抑制。然而，CIEE对海马神经生理学的影响是时间依赖性的。具体而言，在12天无乙醇期后从CIEE处理大鼠记录的神经元与CISE处理动物的神经元具有相似的最大抑制作用，尽管CIEE处理大鼠的神经元达到抑制的时间明显更长。
青春期慢性乙醇暴露会导致对乙醇诱导的海马锥体神经活动抑制的降低或耐受。尽管在12天无乙醇期后这种耐受作用大大逆转，但CIEE动物的神经元比CISE动物的神经元抑制得更慢。由于已知海马体不仅参与空间记忆，还参与许多其他类型记忆的形成,青春期CIEE导致的海马功能改变应被社会视为一个严重警告。
