Roesler Rafael, Kopschina Márcia I, Rosa Renato M, Henriques João Antônio Pêgas, Souza Diogo Onofre, Schwartsmann Gilberto
Preclinical Neuropharmacology Laboratory, Department of Pharmacology, Institute for Basic Health Sciences, and Center for Biotechnology, Federal University of Rio Grande do Sul, Pôrto Alegre, RS, Brazil.
Eur J Pharmacol. 2004 Feb 13;486(1):35-41. doi: 10.1016/j.ejphar.2003.12.011.
Bombesin and its mammalian equivalent, gastrin-releasing peptide (GRP), stimulate cell proliferation and are involved in the pathogenesis of several types of human cancer. Bombesin-like peptides also display neuroendocrine activities and regulate neural function. In the present study, we evaluated the effects of the bombesin/GRP receptor antagonist (D-Tpi(6), Leu(13) psi[CH(2)NH]-Leu(14)) bombesin-(6-14) (RC-3095), experimental antitumor drug, on memory in rats. Adult female Wistar rats were treated with an intraperitoneal injection of RC-3095 (0.2, 1.0 or 5.0 mg/kg) 30 min before training in either inhibitory avoidance or novel object recognition tasks. Retention test trials were carried out 1.5 (short-term memory) or 24 h (long-term memory) after training. RC-3095 at the doses of 0.2 or 1.0 mg/kg, but not at the dose of 5.0 mg/kg, impaired both short- and long-term inhibitory avoidance retention, but did not affect recognition memory. The memory-impairing effect of RC-3095 could not be attributed to alterations in sensorimotor functions. The results show that the antitumor drug/GRP antagonist RC-3095 impairs formation of aversive memory.
蛙皮素及其在哺乳动物中的等效物胃泌素释放肽(GRP)可刺激细胞增殖,并参与多种人类癌症的发病过程。类蛙皮素肽还具有神经内分泌活性并调节神经功能。在本研究中,我们评估了蛙皮素/GRP受体拮抗剂(D-Tpi(6),Leu(13) psi[CH(2)NH]-Leu(14))蛙皮素-(6-14)(RC-3095),一种实验性抗肿瘤药物,对大鼠记忆的影响。成年雌性Wistar大鼠在进行抑制性回避或新物体识别任务训练前30分钟腹腔注射RC-3095(0.2、1.0或5.0 mg/kg)。训练后1.5小时(短期记忆)或24小时(长期记忆)进行记忆保持测试。0.2或1.0 mg/kg剂量的RC-3095损害了短期和长期抑制性回避记忆保持,但不影响识别记忆。RC-3095的记忆损害作用不能归因于感觉运动功能的改变。结果表明,抗肿瘤药物/GRP拮抗剂RC-3095损害厌恶记忆的形成。