Abstract | RATIONALE: OBJECTIVES: In the current study, we have looked into the possible involvement of adult neurogenesis in cognitive restoration by oxotremorine. Further, we have assessed the effect of oxotremorine treatment on depression-like behaviour and hippocampal volumes in stressed animals. METHODS: Chronic restraint stressed rats were treated with either vehicle or oxotremorine. For neurogenesis studies, proliferation, survival and differentiation of the progenitor cells in the hippocampus were examined using 5'-bromo-2-deoxyuridine immunohistochemistry. Depression-like behaviour was evaluated using forced swim test (FST) and sucrose consumption test (SCT). Volumes were estimated using Cavalieri's estimator. RESULTS: Hippocampal neurogenesis was severely decreased in stressed rats. Ten days of oxotremorine treatment to stressed animals partially restored proliferation and survival, while it completely restored the differentiation of the newly formed cells. Stressed rats showed increased immobility and decreased sucrose preference in the FST and SCT, respectively, and oxotremorine ameliorated this depression-like behaviour. In addition, oxotremorine treatment recovered the stress-induced decrease in hippocampal volume. CONCLUSIONS: These results indicate that the restoration of impaired neurogenesis and hippocampal volume could be associated with the behavioural recovery by oxotremorine. Our results imply the muscarinic regulation of adult neurogenesis and incite the potential utility of cholinomimetics in ameliorating cognitive dysfunction in stress-related disorders.
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Authors | J Veena, B N Srikumar, K Mahati, T R Raju, B S Shankaranarayana Rao |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 217
Issue 2
Pg. 239-53
(Sep 2011)
ISSN: 1432-2072 [Electronic] Germany |
PMID | 21494789
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Muscarinic Agonists
- Oxotremorine
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Topics |
- Animals
- Behavior, Animal
(drug effects)
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Depression
(drug therapy, metabolism, psychology)
- Hippocampus
(drug effects, metabolism, pathology)
- Immunohistochemistry
- Male
- Muscarinic Agonists
(therapeutic use)
- Neurogenesis
(drug effects)
- Neurons
(drug effects, pathology)
- Organ Size
(drug effects)
- Oxotremorine
(therapeutic use)
- Rats
- Rats, Wistar
- Restraint, Physical
- Stress, Psychological
(drug therapy, metabolism, psychology)
- Swimming
(psychology)
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