AChR is partly responsible in mice depressive-like behavior after Phosalone exposure

Abstract

Background: Phosalone (Pln) is an organophosphorus pesticide acetylcholinesterase (AChE) inhibitor. Blockade of AChE amplifies ACh signaling that is related to depressive symptoms. The effects of Pln exposure were evaluated on depressive behavior in mice and the involvement of muscarinic ACh receptor (MAChR) was assessed. Material and methods: After measuring total activity in the locomotor test the immobility time during the forced swimming test (FST) in male mice was evaluated as an index of depression. Pln single dose was administered by gavage feeding and examined after 3 h (day1) and on day 7 for evaluating delayed toxicity. In separate groups Pln was administered for 5 consecutive days and examined on day 6 also after one-week delay on day12. Results: While there were only marginal differences in the locomotor tests. Immobility time during the FST significantly increased on day1 by Pln 6, 12, 40 mg/kg (185 +/- 17 s, 186 +/- 9 s, 172.0 +/- 7 s respectively) compared with control animals (149 +/- 8 s, p < 0.01), immobility time was higher than control on day 6 after multiple exposures to Pln (0.6, 6, 12, 20 mg/kg 190 +/- 20s, 210 +/- 4 s, 196 +/- 10s, 204 +/- 9 respectively, vs control 153 +/- 7 p < 0.001). The immobility time remained high following a week of relapse. The co-administration of Pln with scopolamine (Scp) a MAChR antagonist reduced immobility time (141 +/- 10s vs Pln 186 +/- 9 s, p < 0.01). Conclusion: Single exposure to Pln induced depressive-like effects that were reversed by Scp, indicating that MAChR stimulation may be involved. While cumulative exposures caused more pronounced changes in depressive behavior that remained after a week from the last exposure.