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      Malathion induces anxiety in the male adult mouse

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          Abstract

          Introduction

          The cholinergic nervous system and acetylcholine esterase are involved in chronic intoxication with organophosphorous insecticides. The present study aims to investigate the influence of the chronic toxicity of these chemicals on behaviors related to anxiety, using the elevated plus maze (EPM), in the male adult mouse.

          Material and methods

          Either water or 1% concentration of malathion was applied dermally to the male adult mice (10 s, once daily for 28 days) and, on day 29, the EPM test was done.

          Results

          Time spent in the open arms (TSOA) in intoxicated animals was decreased by over 50% compared to the controls ( p = 0.047). In contrast, time spent in closed arms was significantly higher in the malathion-exposed mice ( p = 0.025). Percentage of open arm entries (OAE) was slightly smaller in the malathion-treated group in comparison to the control animals. Percentage of closed arm entries (CAE) in the treated group was slightly higher than the value in the control animals.

          Conclusions

          The results showed that chronic toxicity of malathion may lead to an anxiety-like behavior in the animal model used in this study. It is difficult to extend these findings to clinical situations. However, more experimental work in different animal species as well as epidemiological studies in human subjects in this regard are highly recommended.

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          Most cited references15

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          The use of a plus-maze to measure anxiety in the mouse.

          R Lister (1987)
          To investigate whether an elevated plus-maze consisting of two open and two closed arms could be used as a model of anxiety in the mouse, NIH Swiss mice were tested in the apparatus immediately after a holeboard test. Factor analysis of data from undrugged animals tested in the holeboard and plus-maze yielded three orthogonal factors interpreted as assessing anxiety, directed exploration and locomotion. Anxiolytic drugs (chlordiazepoxide, sodium pentobarbital and ethanol) increased the proportion of time spent on the open arms, and anxiogenic drugs (FG 7142, caffeine and picrotoxin) reduced this measure. Amphetamine and imipramine failed to alter the indices of anxiety. The anxiolytic effect of chlordiazepoxide was reduced in mice that had previously experienced the plus-maze in an undrugged state. Testing animals in the holeboard immediately before the plus-maze test significantly elevated both the percentage of time spent on the open arms and the total number of arm entries, but did not affect the behavioral response to chlordiazepoxide. The plus-maze appears to be a useful test with which to investigate both anxiolytic and anxiogenic agents.
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            The dual role of serotonin in defense and the mode of action of antidepressants on generalized anxiety and panic disorders.

            Antidepressants are widely used to treat several anxiety disorders, among which generalized anxiety disorder (GAD) and panic disorder (PD). Serotonin (5-HT) is believed to play a key role in the mode of action of these agents, a major question being which pathways and receptor subtypes are involved in each type of anxiety disorder. The dual role of 5-HT in defense hypothesis assumes that 5-HT facilitates defensive responses to potential threat, like inhibitory avoidance, related to anxiety, whereas it inhibits defensive responses to proximal danger, like one-way escape, related to panic. The former action would be exerted at the forebrain, chiefly the amygdala and medial prefrontal cortex (PFC), while the latter would be exerted at the dorsal periaqueductal gray (DPAG) matter of the midbrain. The present review is focused on studies designed to test this hypothesis, performed in animal models of anxiety and panic, as well as in human experimental anxiety tests. The reviewed results suggest that chronic, but not acute, administration of antidepressants suppress panic attacks by increasing the release of 5-HT and enhancing the responsivity of post-synaptic 5-HT1A and 5-HT2A receptors in the DPAG. The attenuation of generalized anxiety, also caused by the same drug treatment, would be due to the desensitization of 5-HT2C receptors and, less certainly, to increased stimulation of 5-HT1A receptors in forebrain structures. This action would result in less activation of the amygdala, medial PFC and insula by warning signals, as shown by the reviewed results obtained with functional neuroimaging in healthy volunteers and patients with anxiety disorders.
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              Anxiety associated with exposure to organophosphate compounds.

              Acute organophosphate poisoning is known to result in substantial behavioral abnormalities. We assessed psychiatric manifestations of exposure in workers less substantially exposed to organophosphate compounds and showing no obvious signs of toxicity. Commercial pesticide sprayers and farmers recently exposed to organophosphate agents were compared to control subjects on personality tests, a structured interview, and cholinesterase level. The commercial sprayers but not the exposed farmers showed elevated of anxiety and lower plasma cholinesterase than control subjects. Assessment of other behavioral manifestations and red blood cell cholinesterase failed to disclose other group differences. These findings are viewed as tentative until confirmed by additional study, but they point to the possibility that organophosphate compounds may produce subtle defects in workers who are not obviously toxic. The findings do not justify public alarm but do suggest an area warranting more systematic and definitive investigation.
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                Author and article information

                Journal
                Arch Med Sci
                Arch Med Sci
                AMS
                Archives of Medical Science : AMS
                Termedia Publishing House
                1734-1922
                1896-9151
                10 February 2013
                20 April 2013
                : 9
                : 2
                : 368-371
                Affiliations
                [1 ]Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
                [2 ]Faculty of Veterinary Medicine, Islamic Azad University – Tabriz Campus, Tabriz, Iran
                Author notes
                Corresponding author: Goudarz Sadeghi Hashjin PhD, Faculty of Veterinary Medicine, University of Tehran, P.O. Box 6453, Tehran 14155 Iran. Phone: +98 21 611 171 90. Fax: +98 21 669 332 22. E-mail: gsadeghi@ 123456ut.ac.ir
                Article
                20239
                10.5114/aoms.2013.33174
                3648820
                23671451
                5ae41f15-297c-4524-bd80-f7e6ba7873e7
                Copyright © 2013 Termedia & Banach

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 November 2010
                : 15 September 2011
                : 08 December 2011
                Categories
                Experimental Research

                Medicine
                anxiety,elevated plus maze,malathion,mouse,organophosphates
                Medicine
                anxiety, elevated plus maze, malathion, mouse, organophosphates

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