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A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
Published on: May 15, 2019
Potential role of a newly AChE reactivator in the depressive-like behavior induced by malathion
Anne Suély Pinto Savall1, Eduarda Monteiro Fidelis1, Caroline Brandão Quines1
1Federal University of Pampa - Campus Uruguaiana, Uruguaiana, ZIP code 97500-970, RS, Brazil.
Abstract:
AChE inhibition caused by exposure to organophosphate (OP) compounds is strongly related to behavioural disorders such as depression. Malathion is an OP that already has a relationship between its exposure and behavioural changes, although few data still have its effects in a longer exposure protocol. In addition, intoxication therapy is based on the use of atropine-oxime which still has its controversial efficacy depending on the type of compound. For this, (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one (Cℓ-HIN), a compound that has properties of isatin and oxime in its structure, have shown reactivating properties in the activity of AChE that have been added to antidepressant-like effects in rats exposed to malathion in acute protocol. In this sense, effects of Cℓ-HIN on the depressive-like behaviour and AChE activity were evaluated in a protocol of subchronic exposure to malathion in rats. Male wistar rats were co-treated with Cℓ-HIN [5 mg/kg, p.o.] and/or malathion [1 or 10 mg/kg, i.p] for 20 days. The exposure to both doses of malathion increased immobility time of rats on the forced swimming test (FST). Besides, malathion inhibited the AChE activity in the prefrontal cortex of rats, but any significant difference was observed in the hippocampus. Cℓ-HIN protected against increased immobility time in the FST of those rats exposed to a dose of 1 mg/kg of malathion. Similarly, Cℓ-HIN was able to reactivate AChE activity only in that group exposed to the lowest dose of malathion. Collectively, the results of this study suggest that Cℓ-HIN is an oxime capable of reactivating AChE inhibited and presents na antidepressant-like effect in cases of prolonged exposure to malathion.
Insights
Organophosphate (OP) exposure, like malathion, can cause depression. The compound (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one (Cℓ-HIN) showed antidepressant-like effects and reactivated acetylcholinesterase (AChE) in rats with prolonged malathion exposure.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Organophosphate (OP) compounds, such as malathion, are known to inhibit acetylcholinesterase (AChE), leading to behavioral disorders like depression.
- The efficacy of current antidotes like atropine-oxime is controversial, necessitating the development of novel therapeutic agents.
- Previous studies indicated that (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one (Cℓ-HIN) possesses AChE reactivating and antidepressant-like properties in acute malathion exposure models.
Purpose of the Study:
- To investigate the effects of Cℓ-HIN on depressive-like behavior and AChE activity in rats following subchronic exposure to malathion.
- To evaluate the potential of Cℓ-HIN as a therapeutic agent for prolonged OP intoxication.
Main Methods:
- Male Wistar rats were co-treated with Cℓ-HIN (5 mg/kg, p.o.) and malathion (1 or 10 mg/kg, i.p.) for 20 days.
- Depressive-like behavior was assessed using the forced swimming test (FST).
- AChE activity was measured in the prefrontal cortex and hippocampus.
Main Results:
- Subchronic exposure to both doses of malathion significantly increased immobility time in the FST, indicating depressive-like behavior.
- Malathion inhibited AChE activity in the prefrontal cortex but not the hippocampus.
- Cℓ-HIN treatment attenuated the increased immobility time in rats exposed to the lower dose of malathion (1 mg/kg) and reactivated AChE activity in this group.
Conclusions:
- Cℓ-HIN demonstrates antidepressant-like effects and AChE reactivating properties in a subchronic malathion exposure model.
- These findings suggest Cℓ-HIN as a potential therapeutic candidate for managing prolonged organophosphate intoxication.
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