Dulawa S C, Hen R, Scearce-Levie K, Geyer M A
Department of Neuroscience, University of California at San Diego, La Jolla 92093-0804, USA.
Psychopharmacology (Berl). 1997 Jul;132(2):125-34. doi: 10.1007/s002130050328.
Two operational measures of central information processing mechanisms are habituation and prepulse inhibition (PPI) of the startle response. Both measures can be assessed reliably in humans and other animals, and have been shown to be deficient in patients with schizophrenia. The three present experiments assessed the involvement of the serotonin1B (5-HT1B) receptor in modulating startle reactivity, habituation, and PPI by comparing 5-HT1B receptor gene knockout (5-HT1B knockout) with wild-type 129/Sv mice. In experiment I, female mice received saline, 2.0 mg/kg 5-methoxy-3(1,2,3,6)tetrahydropyridin-4-yl-1H-indole (RU24969), a 5-HT1A/1B agonist, and 1.0 mg/kg 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A agonist. Female mice received saline, 10.0 mg/kg RU24969, and 5.0 mg/kg 8-OH-DPAT in experiment 2, and male mice received saline, 10.0 mg/kg RU24969, and 5.0 mg/kg 8-OH-DPAT in experiment 3. All three studies used identical within-subjects designs. Two phenotypic differences were observed following saline treatment: 5-HT1B knockout mice consistently exhibited a small increase in PPI that achieved significance in experiment 1; and 5-HT1B knockout male mice exhibited robust decreases in startle reactivity. Habituation was disrupted consistently by RU24969 in wild-type but not in 5-HT1B knockout mice, while 8-OH-DPAT had no effect on habituation. Consistent with the phenotypic difference in PPI, the high dose of RU24969 significantly and consistently reduced PPI in wild-type but not in 5-HT1B knockout mice. 8-OH-DPAT increased PPI in both wild-type and 5-HT1B knockout mice in every experiment. These findings suggest that 5-HT1B receptors modulate startle reactivity, habituation, and PPI in mice. Additionally, a potential species difference may exist in the behavioral effects of 5-HT1A receptor activation on PPI.
中枢信息处理机制的两项操作性测量指标是习惯化和惊吓反应的前脉冲抑制（PPI）。这两项测量指标在人类和其他动物中都能得到可靠评估，并且已证实在精神分裂症患者中存在缺陷。目前的三个实验通过比较5-羟色胺1B（5-HT1B）受体基因敲除（5-HT1B敲除）小鼠和野生型129/Sv小鼠，评估了5-HT1B受体在调节惊吓反应性、习惯化和PPI中的作用。在实验I中，雌性小鼠接受生理盐水、2.0毫克/千克5-甲氧基-3（1,2,3,6）四氢吡啶-4-基-1H-吲哚（RU24969，一种5-HT1A/1B激动剂）以及1.0毫克/千克8-羟基-2（二正丙基氨基）四氢萘（8-OH-DPAT，一种选择性5-HT1A激动剂）。在实验2中，雌性小鼠接受生理盐水、10.0毫克/千克RU24969以及5.0毫克/千克8-OH-DPAT；在实验3中，雄性小鼠接受生理盐水、10.0毫克/千克RU24969以及5.0毫克/千克8-OH-DPAT。所有三项研究均采用相同的受试者内设计。在生理盐水处理后观察到两个表型差异：5-HT1B敲除小鼠的PPI持续出现小幅增加，在实验1中达到显著水平；5-HT1B敲除雄性小鼠的惊吓反应性显著降低。在野生型小鼠中，RU24969持续破坏习惯化，但在5-HT1B敲除小鼠中则不然，而8-OH-DPAT对习惯化没有影响。与PPI中的表型差异一致，高剂量的RU24969在野生型小鼠中显著且持续降低PPI，但在5-HT1B敲除小鼠中则不然。在每个实验中，8-OH-DPAT在野生型和5-HT1B敲除小鼠中均增加PPI。这些发现表明，5-HT1B受体调节小鼠的惊吓反应性、习惯化和PPI。此外，5-HT1A受体激活对PPI的行为影响可能存在潜在的物种差异。
