Nikulina E M, Marchand J E, Kream R M, Miczek K A
Department of Psychology, Tufts University, Medford, MA, USA.
Brain Res. 1998 Nov 9;810(1-2):200-10. doi: 10.1016/s0006-8993(98)00925-1.
The objective of the present study was to determine how c-fos gene expression in brainstem structures after a brief episode of social defeat stress is related to behavioral sensitization to cocaine challenge. Social stress was defined as defeat in a brief confrontation with an aggressive resident mouse and subsequent 20-min exposure to the resident's threats behind a protective screen. Mice were treated with cocaine (40 mg/kg, i.p.) immediately or 1 week after social defeat stress. Fos-like immunoreactive (Fos-LI) cell nuclei were analyzed in the ventral tegmental area (VTA), dorsal raphe nucleus (DR), periaqueductal grey area (PAG) and locus coeruleus (LC). One episode of social stress induced behavioral sensitization to cocaine as indicated by an augmented locomotor response to a challenge injection 7 days after a single defeat. In naive mice, social stress markedly increased the number of Fos-LI nuclei in the DR, PAG and LC, but not in the VTA. Similarly, cocaine administration resulted in a significantly increased number of Fos-LI nuclei in the same areas. Administration of cocaine immediately following social defeat significantly reduced the number of Fos-LI nuclei in the DR, PAG and LC. Cocaine-induced Fos expression returned in the PAG and DR, but not in the LC, 1 week after social stress. In conclusion, the present results suggest that the presence of brainstem Fos be related to the ability to express stress-induced behavioral sensitization to cocaine.
本研究的目的是确定短暂的社会挫败应激后脑干结构中c-fos基因表达与对可卡因激发的行为敏化之间的关系。社会应激被定义为在与具有攻击性的常驻小鼠的短暂对抗中失败，随后在保护屏后暴露于常驻小鼠的威胁下20分钟。小鼠在社会挫败应激后立即或1周后接受可卡因（40mg/kg，腹腔注射）治疗。分析腹侧被盖区（VTA）、中缝背核（DR）、导水管周围灰质区（PAG）和蓝斑（LC）中Fos样免疫反应性（Fos-LI）细胞核。一次社会应激诱导了对可卡因的行为敏化，单次挫败后7天对激发注射的运动反应增强即表明了这一点。在未经历过应激的小鼠中，社会应激显著增加了DR、PAG和LC中Fos-LI细胞核的数量，但VTA中没有增加。同样，给予可卡因也导致相同区域中Fos-LI细胞核数量显著增加。社会挫败后立即给予可卡因显著减少了DR、PAG和LC中Fos-LI细胞核的数量。社会应激1周后，可卡因诱导的Fos表达在PAG和DR中恢复，但在LC中未恢复。总之，目前的结果表明脑干Fos的存在与表达应激诱导的对可卡因行为敏化的能力有关。
