Change in atropine dose effect curve after subacute soman administration

Thirty-one adult male rats were trained on a two component (FR10-extinction) operant task. After establishment of an atropine sulfate dose effect curve (vehicle, 1.0, 1.8, 3.2, 5.6 or 10.0 mg/kg), all rats were injected SC with 35.0 micrograms/kg soman three times per week for four weeks. One, twenty-eight and fifty-six days after the last soman injection, additional atropine tests were given. Atropine produced significant dose related decreases in FR10 responding at 3.2, 5.6 and 10.0 mg/kg during the initial dose effect curve with no effect on extinction responding. Although four rats died during the soman exposure period, the remaining rats exhibited neither signs of organophosphate toxicity nor significant disruptions in FR responding. However, a significant increase in extinction component responding was seen on soman injection days. The atropine dose effect curve for FR10 responding showed a significant shift to the left on the day after the last dose of soman. However, the dose effect curves at 4 and 8 weeks were the same as the initial curve. These results provide behavioral evidence that chronic soman exposure results in a supersensitivity to the antimuscarinic drug, atropine, possibly due to a down-regulation in the number of muscarinic receptors.