BEHAVIORAL-COMPARISON OF THE OXIMES TMB-4, 2-PAM, AND HI-6 IN RATS USING OPERANT-CONDITIONING

It has recently been shown that oximes can amplify the ability of chol inesterases to scavenge organophosphorus (OF) agents. Since both OP ag ents and oximes can disrupt performance, behavioral evaluation of bios cavenger therapies using oximes can be hindered. Therefore, we investi gated the ability of three oximes, administered alone, to disrupt perf ormance. The effects of trimedoxime bromide (TMB-4) (3.16-56.2 mg/kg), pralidoxime chloride (2-PAM) (10.0-237.1 mg/kg), and, -([[4-amincarbo nyl)pyridino]-methoxy]-methyl)-2,4- bis[(hydroxyimino)methyl] pyridini um dichloride monohydrate (HI-6) (10.0-237.1 mg/kg) were evaluated in rats using a variable-interval 56 (VI 56) s schedule of food reinforce ment. Under control conditions, the VI 56 a schedule produced a consta nt rate of responding (i.e., lever-pressing). All three oximes produce d dose-dependent decreases in responding, and the largest doses of TMB -4 and 2-PAM produced complete or nearly complete suppression of respo nding in all rats. Only the largest dose of HI-6 suppressed responding . Analysis of the dose-effect functions demonstrated that TMB-4 was su bstantially more potent than 2-PAM, which was slightly more potent tha n HI-6, for producing response suppression. These results establish do ses of each oxime that will not contribute to disruption of responding , and thus, facilitate future evaluation of bioscavenger therapies aga inst OP toxicity.