Related Experiment Video
Updated: Aug 6, 2026
The 5-Choice Serial Reaction Time Task: A Task of Attention and Impulse Control for Rodents
Published on: August 10, 2014
Short-term effects of paraoxon and atropine on schedule-controlled behavior in rats
1Department of Biological Sciences, Mississippi State University, MS 39762.
Abstract:
The effects of lethal (2.0 mg/kg) and high sublethal (1.3 mg/kg) dosages of the organophosphate acetylcholinesterase (AChE) inhibitor paraoxon on FR10 performance rate was determined 1 and 2 days after intoxication. The lethal doses were antidoted with either centrally acting atropine sulfate (AS), or atropine methyl bromide (AMB) or atropine methyl nitrate (AMN), both quaternary salts and not expected to act centrally. AChE inhibition in the brain was about 35-60% on the second day after treatment. AS yielded a small transient depression in performance, while AMB and AMN yielded severe deficits, with incomplete recovery. Performance was depressed by 1.3 mg/kg paraoxon by 52% and 34% on days 1 and 2, respectively, while performance was more greatly depressed by the lethal dose, especially with the noncentrally acting antidotes: AS, 67 and 48%; AMB, 81 and 55%; AMN, 91 and 78%. However, a low dose of AS with 2 mg/kg paraoxon resulted in very severe, nonrecovering deficits. A lethal dose of the nonpersistent anti-AChE eserine sulfate, antidoted with a low dose of AS, yielded no deficits. Thus, a high level, acute intoxication with paraoxon yields behavioral deficits which are attenuated by high levels of a centrally acting muscarinic receptor antagonist. The paraoxon-induced performance deficits or their recovery do not correlate directly with AChE inhibition.
Insights
Organophosphate paraoxon causes performance deficits, with centrally acting atropine sulfate offering some recovery. Non-centrally acting antidotes worsened deficits, suggesting central mechanisms in organophosphate toxicity.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Organophosphate pesticides, like paraoxon, are potent acetylcholinesterase (AChE) inhibitors.
- Paraoxon intoxication can lead to significant behavioral impairments.
- The role of central versus peripheral muscarinic receptor antagonism in paraoxon toxicity is not fully understood.
Purpose of the Study:
- To investigate the effects of paraoxon on performance rate.
- To evaluate the efficacy of centrally and non-centrally acting antidotes in mitigating paraoxon-induced deficits.
- To explore the relationship between AChE inhibition levels and behavioral recovery.
Main Methods:
- Rats were administered lethal (2.0 mg/kg) and sublethal (1.3 mg/kg) doses of paraoxon.
- Intoxicated rats were treated with atropine sulfate (centrally acting) or atropine methyl bromide/nitrate (non-centrally acting).
- Performance rate (FR10) was assessed 1 and 2 days post-intoxication; brain AChE inhibition was measured.
Main Results:
- Paraoxon significantly depressed performance, with higher doses causing greater deficits.
- Centrally acting atropine sulfate provided partial recovery, while non-centrally acting quaternary salts resulted in severe, persistent deficits.
- Behavioral deficits did not directly correlate with the degree of brain AChE inhibition.
Conclusions:
- Acute paraoxon intoxication causes significant behavioral deficits.
- Centrally acting muscarinic antagonists attenuate paraoxon-induced performance deficits.
- Central cholinergic pathways are critical in mediating the behavioral effects of paraoxon.
