Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago Medical School, P.O. Box 913, Dunedin, New Zealand.
Neurobiol Learn Mem. 2010 Oct;94(3):402-13. doi: 10.1016/j.nlm.2010.08.007. Epub 2010 Aug 22.
Previous studies of rats with bilateral vestibular deafferentation (BVD) have demonstrated spatial memory deficits, suggesting adverse effects on the hippocampus. However, the longest post-operative time interval that has been studied was approx. 5-7 months post-surgery. In this study, we investigated whether rats exhibited spatial memory deficits at 14 months following BVD and whether these deficits could be exacerbated by administration of cannabinoid (CB) drugs. Twenty-eight adult rats were divided into four groups: (1) sham surgery+vehicle; (2) sham surgery+the CB1/CB(2) receptor agonist WIN55,212-2 ('WIN'); (3) BVD+vehicle; and (4) BVD+WIN. WIN (1.0 or 2.0 mg/kg/day) or vehicle, was administered (s.c.) on days 1-10 and 11-20 (respectively), 30 min before the rats performed in a foraging task. On day 21, the CB receptor inverse agonist, AM251 (3.0 mg/kg, s.c.), was administered before WIN or vehicle. To our surprise, BVD animals were impaired in using the visual cues during the probe test in light. In the dark trials, when visual cues were unavailable, BVD animals were unable to use self-movement cues in homing. However, WIN at 2 mg/kg, significantly improved BVD animals' homing time and number of errors in the dark through strategies other than the improvement in using self-movement cues. Furthermore, AM251 significantly improved heading angle in vehicle-treated animals and the first home choice in WIN-treated animals. These results suggest that at 14 months post-BVD, the animals are not only impaired in path integration, but also piloting and that the spatial memory deficits may be permanent. The involvement of the cannabinoid system is more complicated than expected.
先前对双侧前庭去传入（BVD）大鼠的研究表明，空间记忆缺陷表明对海马体有不利影响。然而，研究的最长术后时间间隔约为术后 5-7 个月。在这项研究中，我们研究了 BVD 后 14 个月大鼠是否表现出空间记忆缺陷，以及这些缺陷是否会因大麻素（CB）药物的给药而加剧。28 只成年大鼠被分为四组：（1）假手术+载体；（2）假手术+CB1/CB2 受体激动剂 WIN55,212-2（“WIN”）；（3）BVD+载体；和（4）BVD+WIN。WIN（1.0 或 2.0 mg/kg/天）或载体，分别于第 1-10 天和第 11-20 天（分别）给药（皮下），在大鼠进行觅食任务前 30 分钟给药。在第 21 天，给予 CB 受体反向激动剂 AM251（3.0 mg/kg，皮下），然后给予 WIN 或载体。令我们惊讶的是，BVD 动物在探针测试中在光线下使用视觉线索受损。在黑暗试验中，当没有视觉线索时，BVD 动物无法在家中使用自身运动线索。然而，WIN 以 2 mg/kg 的剂量，通过改善自身运动线索以外的策略，显著改善了 BVD 动物在黑暗中的归巢时间和错误次数。此外，AM251 显著改善了载体处理动物的航向角和 WIN 处理动物的首次归巢选择。这些结果表明，在 BVD 后 14 个月，动物不仅在路径整合方面受损，而且在领航方面也受损，空间记忆缺陷可能是永久性的。大麻素系统的参与比预期的更复杂。
