Ohdo S, Yoshimura H, Ogawa N
Department of Pharmacology, Ehime University School of Medicine, Japan.
Psychopharmacology (Berl). 1989;97(1):30-4. doi: 10.1007/BF00443408.
We investigated how repeated agonistic confrontations affect the hypnotic effect of pentobarbital (PB) in male mice, using a resident-intruder paradigm. PB concentrations in the cortex, midbrain and brainstem were determined. Agonistic confrontations were terminated after 10 or 20 attack bites, and were repeated for 5 consecutive days. Immediately after the last encounter, PB (55 mg/kg, IP) was administered to both resident and intruder mice. Compared to the control group, intruders exposed to 20 daily attack bites showed a significant prolongation of the latency to sleep and a shortening of the duration of sleeping time. At the stage of induction, no significant difference in brain PB levels was found between the "defeated" and control intruders. At the stage of recovery, however, the "defeated" intruders showed a significantly low level of PB in all brain areas. In contrast, attacking resident mice did not show any significant changes in either the hypnotic effect or regional brain concentration of PB. Because pretreatment with naloxone prior to daily agonistic confrontation antagonized the alteration in PB-induced hypnosis, it seems that endogenous opioid mechanisms may participate in this phenomenon. The present study indicates that susceptibility to a hypnotic drug can be altered by chronic social conflict experience.
我们采用定居者-入侵者范式，研究了反复的攻击性对抗如何影响雄性小鼠中戊巴比妥（PB）的催眠效果。测定了皮质、中脑和脑干中的PB浓度。在10次或20次攻击撕咬后终止攻击性对抗，并连续重复5天。在最后一次对抗后立即给定居者和入侵者小鼠腹腔注射PB（55mg/kg）。与对照组相比，每天遭受20次攻击撕咬的入侵者睡眠潜伏期显著延长，睡眠时间缩短。在诱导阶段，“战败”入侵者和对照入侵者的脑PB水平无显著差异。然而，在恢复阶段，“战败”入侵者在所有脑区的PB水平显著降低。相比之下，具有攻击性的定居者小鼠在PB的催眠效果或脑区浓度方面均未表现出任何显著变化。由于在每日攻击性对抗前用纳洛酮预处理可拮抗PB诱导催眠的改变，内源性阿片机制似乎可能参与了这一现象。本研究表明，慢性社会冲突经历可改变对催眠药物的敏感性。
