Hippocampal Gene Expression in bred High Responder (bHR) vs. bred Low Responder (bLR) Rats: Affymetrix Microarray Data from Generation F4

The strong pattern of comorbidity amongst psychiatric disorders is believed to be generated by a spectrum of latent liability, arising from a complex interplay of genetic risk and environmental factors, such as stress and childhood adversity. At one end of this spectrum are internalizing disorders, which are associated with neuroticism, anxiety, and depression. At the other end of the spectrum are externalizing disorders, which are associated with risk-taking and novelty-seeking, as seen in mania, substance abuse, and impulse-control disorders. We model the genetic contributions underlying both extremes of this spectrum by selectively breeding rats that react differently to a novel environment. “Bred high responder” (bHR) rats are highly exploratory with a disinhibited, novelty-seeking temperament, including hyperactivity, aggression, and drug-seeking. “Bred low responder” (bLR) rats are highly-inhibited, exhibiting reduced locomotor activity and anxious and depressive-like behavior. These behavioral propensities are robust and stable, beginning early in development similar to temperament in humans. This Affymetrix (Rat Expression Set 230 A) microarray study examined gene expression in the hippocampus in generation F4 adult male bHR rats and bLR rats (n=6 per group).学界普遍认为，精神障碍间显著的共病模式由一系列潜在易感性谱所驱动，该谱源于遗传风险与应激、童年逆境等环境因素的复杂交互作用。 该谱的一端为内化性障碍（internalizing disorders），与神经质、焦虑及抑郁症状相关。 另一端则为外化性障碍（externalizing disorders），与冒险行为、寻求新奇特质相关，常见于躁狂、物质滥用及冲动控制障碍中。 本研究通过对新型环境刺激反应不同的大鼠进行选择性繁育，以此为该谱极端两端的遗传贡献构建模型。 繁育高反应型（bHR）大鼠具有高度探索性，表现出去抑制、寻求新奇的气质特征，包括多动、攻击行为及药物觅求行为。 繁育低反应型（bLR）大鼠则表现出高度抑制性，活动能力降低，并呈现焦虑样与抑郁样行为。 这些行为倾向具有稳定性与持久性，且在发育早期即已显现，与人类的气质特征类似。 本研究采用Affymetrix公司（大鼠表达谱芯片Set 230 A）进行微阵列分析，检测了第4代（F4）成年雄性繁育高反应型与低反应型大鼠海马组织的基因表达水平，每组样本量为6只。