Harro J, Oreland L, Vasar E, Bradwejn J
Department of Pharmacology, University of Tartu, Estonia.
Eur Neuropsychopharmacol. 1995 Dec;5(4):447-55. doi: 10.1016/0924-977x(95)00015-h.
The effect of DSP-4, a neurotoxin selectively affecting the projections of the locus coeruleus, upon exploratory behaviour of rats was studied in a complex exploration test, including a choice between open and enclosed areas and both inquisitive and inspective exploration elements. One week after DSP-4 (50 mg/kg i.p.) administration, the neurotoxin-treated rats did not explore a novel open area to any extent on the first exposure to the apparatus; however, on the third day of testing, these animals began to explore the area and the novel objects. Diazepam (0.5 mg/kg) treatment did not change the behaviour of control rats, but significantly increased the exploratory activity of the DSP-4-treated animals. LY 288513, a selective CCKB receptor antagonist (0.01 mg/kg), prevented the increase in exploratory activity in the DSP-4-treated rats, but increased the exploratory activity of controls on the third exposure to the test situation. The results of this investigation suggest that DSP-4 treatment reduces neotic behaviour by increasing neophobia rather than by decreasing exploratory drive. The divergence reported between the relative potencies of CCKB receptor antagonists in exploratory activity and other anxiety tests may in part be due to the effects of these drugs on exploratory drive.
研究了DSP-4（一种选择性影响蓝斑投射的神经毒素）对大鼠探索行为的影响，采用了一种复杂的探索试验，包括在开放区域和封闭区域之间进行选择，以及好奇探索和仔细观察探索元素。腹腔注射DSP-4（50mg/kg）一周后，经神经毒素处理的大鼠在首次接触该装置时并未对新的开放区域进行任何程度的探索；然而，在测试的第三天，这些动物开始探索该区域和新物体。地西泮（0.5mg/kg）处理并未改变对照大鼠的行为，但显著增加了经DSP-4处理动物的探索活动。LY 288513（一种选择性CCKB受体拮抗剂，0.01mg/kg）可阻止经DSP-4处理大鼠的探索活动增加，但在第三次接触测试情境时增加了对照大鼠的探索活动。本研究结果表明，DSP-4处理通过增加新事物恐惧而非降低探索驱动力来减少新奇行为。CCKB受体拮抗剂在探索活动和其他焦虑测试中的相对效力之间所报告的差异可能部分归因于这些药物对探索驱动力的影响。
