Behaviorally augmented versus other components in organophosphate tolerance: the role of reinforcement and response factors.

Male Wistar-derived rats were used to assess the behaviorally augmented component of tolerance to paraoxon depression of a feeding response. Separate groups of animals were treated daily by 0.125 mg/kg of the compound given sc either 1 hr before the start or 45 min after the end of a 90-min feeding session. However, the dose was reduced to 0.0625 mg/kg from Day 9 to Day 12 of the treatment series if animals showed too severe a reduction in food consumption. After development of tolerance by the presession treatment group, the animals treated after feeding were shifted to treatment before feeding. This shift produced a marked depression in food consumption. This confirms similar data previously obtained by a different test (two-way avoidance), and indicates that behaviorally augmented tolerance to paraoxon related to practice factors may be a fairly general phenomenon. Other experiments were to assess the effects of paraoxon in the conditioned taste aversion (CTA) paradigm. These showed the development of an aversion only at high dosage levels (two pairings between the flavor cue and 0.25 mg/kg sc, or four pairings with a 0.17-mg/kg dose). However, the failure of lower doses to produce CTA may have depended on the relatively slow onset of the intoxication, producing an extended interval between the end of cue exposure and the development of malaise or illness. Two pretreatments given 6 and 3 days before the first conditioning session in an experiment using the 2 X 0.25-mg/kg schedule did not affect the development of CTA as measured by a conventional double-bottle test. However, a typical interference effect produced by prior exposure was shown by a substantial acceleration of subsequent CTA extinction in pretreated animals.