title: Evidence that spatial memory deficits following bilateral vestibular deafferentation in rats are probably permanent.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago Medical School, P.O. Box 913, Dunedin, New Zealand.
authors.forename: Jean Ha
authors.initials: JH
authors.lastname: Baek
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Zheng
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Darlington
authors.forename: Paul F
authors.initials: PF
authors.lastname: Smith
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D048588:Benzoxazines / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008569:Memory Disorders / Q000503:physiopathology*; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D014722:Vestibule, Labyrinth / Q000293:injuries*
chemical_list: D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone