Time course of behavioral changes following basal forebrain cholinergic damage in rats: Environmental enrichment as a therapeutic intervention.
The present experiment was designed to study changes in behavior following immunolesioning of the basal forebrain cholinergic system. Rats were lesioned at 3 months of age by injection of the 192 IgG-saporin immunotoxin into the medial septum area and the nucleus basalis magnocellularis, and then tested at different times after surgery (from days 7-500) on a range of behavioral tests, administered in the following order: a nonmatching-to-position task in a T-maze, an object-recognition task, an object-location task, and an open-field activity test. The results revealed a two-way interaction between post-lesion behavioral testing time and memory demands. In the nonmatching-to-position task, memory deficits appeared quite rapidly after surgery, i.e. at a post-lesion time as short as 1 month. In the object-recognition test, memory impairments appeared only when rats were tested at late post-lesion times (starting at 15 months), whereas in the object-location task deficits were apparent at early post-lesion times (starting from 2 months). Taking the post-operative time into account, one can hypothesize that at the shortest post-lesion times, behavioral deficits are due to pure cholinergic depletion, while as the post-lesion time increases, one can speculate the occurrence of a non-cholinergic system decompensation process and/or a gradual degeneration process affecting other neuronal systems that may contribute to mnemonic impairments. Interestingly, when middle-aged rats were housed in an enriched environment, 192 IgG-saporin-lesioned rats performed better than standard-lesioned rats on both the nonmatching-to-position and the object-recognition tests. Environment enrichment had significant beneficial effects in 192 IgG-saporin-lesioned rats, suggesting that lesioned rats at late post-lesion times (over 1 year) still have appreciable cognitive plasticity.
Paban
V
V
Université d'Aix-Marseille I, Laboratoire de Neurobiologie Intégrative et Adaptative, UMR/CNRS 6149, Avenue Normandie Escadrille Niemen, 13397 Marseille, Cedex 20, France. paban@up.univ-mrs.fr
Jaffard
M
M
Chambon
C
C
Malafosse
M
M
Alescio-Lautier
B
B
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D020532:Basal Nucleus of Meynert / Q000473:pathology / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D002799:Cholinergic Fibers / Q000378:metabolism / Q000473:pathology*; D003714:Denervation; D004195:Disease Models, Animal; D004779:Environment Design; D000922:Immunotoxins; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009699:N-Glycosyl Hydrolases; D009473:Neuronal Plasticity / Q000502:physiology; D009498:Neurotoxins; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000502:physiology; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012686:Septal Nuclei / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D009498:Neurotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D000109:Acetylcholine