全身及伏隔核内注射苯丙胺后惊跳前脉冲抑制破坏中的品系差异。
Strain differences in the disruption of prepulse inhibition of startle after systemic and intra-accumbens amphetamine administration.
作者信息
Swerdlow Neal R, Shoemaker Jody M, Bongiovanni Michele J, Neary Alaina C, Tochen Laura S, Saint Marie Richard L
机构信息
Department of Psychiatry, UCSD School of Medicine, La Jolla, CA 92093-0804, USA.
出版信息
Pharmacol Biochem Behav. 2007 May;87(1):1-10. doi: 10.1016/j.pbb.2007.03.014. Epub 2007 Apr 3.
BACKGROUND
Sprague Dawley (SD) rats are significantly more sensitive than Long Evans (LE) rats to the disruption of prepulse inhibition (PPI) by systemically-administered dopamine (DA) agonists. This strain difference is heritable and insensitive to cross-fostering. Inherited differences in the ability of elevated DA activity to disrupt PPI may be useful for understanding the neural basis for PPI deficits in schizophrenia and other neuropsychiatric disorders.
METHODS
PPI was tested in male SD and LE rats after amphetamine (AMPH) was administered: 1) subcutaneously (sc), or intra-cerebrally (ic) into 2) the nucleus accumbens core (NACc; medial or lateral subregions) or the NAC shell; 3) the anteromedial striatum (AMS) or 4) the posterior striatum (PS).
RESULTS
SD and LE rats had comparable PPI levels after sc vehicle injection. PPI was disrupted in SD but not LE rats after sc AMPH injection. LE insensitivity to AMPH was confirmed after sc injection into non-pigmented dermis, demonstrating that it did not reflect melanocyte sequestration of AMPH. PPI was also disrupted in SD rats after ic infusion into the NACc (medial core: p<0.005; lateral core: p<0.001); in LE rats, these effects only approached threshold levels (medial core: p<0.06; lateral core: p<0.051). In SD rats, the highest dose of AMPH (40 microg) tended to reduce PPI after infusion into the AMS or PS, while in LE rats, this dose potentiated PPI after PS infusion. Comparisons of PPI in SD vs. LE rats revealed significant main effects of strain (SD>LE) after vehicle infusions into the NACc subregions and the PS. Comparisons of pre-infusion "matching" data, data from the first infusion day, and data from separate rats in a "mock-infusion" paradigm is consistent with the possibility that SD>LE PPI after ic vehicle infusion reflects the impact of restraint stress on PPI in LE rats.
CONCLUSIONS
PPI is disrupted by AMPH administered sc or into the NACc in SD but not LE rats. Reduced PPI after ic vehicle infusion in LE vs. SD rats may reflect greater PPI-reducing effects of restraint stress in LE rats. The differential impact of restraint on PPI in SD vs. LE rats complicates the interpretation of strain differences in the effects of ic manipulations, but may provide an avenue for investigating the basis for differences in vulnerability to the gating-disruptive effects of stress.
背景
与长 Evans（LE）大鼠相比，斯普拉格-道利（SD）大鼠对全身给药的多巴胺（DA）激动剂破坏前脉冲抑制（PPI）的作用更为敏感。这种品系差异具有遗传性，且不受交叉寄养的影响。多巴胺活性升高破坏 PPI 能力的遗传差异，可能有助于理解精神分裂症和其他神经精神疾病中 PPI 缺陷的神经基础。
方法
在给雄性 SD 和 LE 大鼠注射苯丙胺（AMPH）后测试 PPI：1）皮下（sc）或脑内（ic）注射到 2）伏隔核核心（NACc；内侧或外侧亚区）或 NAC 壳；3）前内侧纹状体（AMS）或 4）后内侧纹状体（PS）。
结果
皮下注射溶剂后，SD 和 LE 大鼠的 PPI 水平相当。皮下注射 AMPH 后，SD 大鼠的 PPI 受到破坏，而 LE 大鼠则未受影响。将 AMPH 注射到非色素性真皮后，证实 LE 大鼠对 AMPH 不敏感，这表明该现象并非由黑素细胞对 AMPH 的隔离所致。向 NACc 脑内注射后，SD 大鼠的 PPI 也受到破坏（内侧核心：p<0.005；外侧核心：p<0.001）；在 LE 大鼠中，这些效应仅接近阈值水平（内侧核心：p<0.06；外侧核心：p<0.051）。在 SD 大鼠中，最高剂量的 AMPH（40 微克）注射到 AMS 或 PS 后往往会降低 PPI，而在 LE 大鼠中，该剂量注射到 PS 后会增强 PPI。比较 SD 和 LE 大鼠的 PPI 发现，向 NACc 亚区和 PS 注射溶剂后，品系有显著的主效应（SD>LE）。对注射前“匹配”数据、首次注射日的数据以及“假注射”范式中不同大鼠的数据进行比较，结果表明脑内注射溶剂后 SD>LE 的 PPI 可能反映了束缚应激对 LE 大鼠 PPI 的影响。
结论
皮下或向 NACc 注射 AMPH 会破坏 SD 大鼠而非 LE 大鼠的 PPI。与 SD 大鼠相比，LE 大鼠脑内注射溶剂后 PPI 降低，可能反映了束缚应激对 LE 大鼠 PPI 的更大降低作用。束缚对 SD 和 LE 大鼠 PPI 的不同影响，使对脑内操作效应的品系差异解释变得复杂，但可能为研究应激对门控破坏作用易感性差异的基础提供一条途径。
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