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S C Helps

Publications and source records attributed to S C Helps.

22 records · Page 2Linked to original sources

Selective breeding for sensitivity to DFP: generalization of effects beyond criterion variables.

The degree of generalization to the effects of DFP, an organophosphate anticholinesterase, was studied in two lines of Sprague-Dawley derived rats selectively bred for varying sensitivities to DFP. In the S13, S14, S15, and S16 generations the Flinders S-line of rats were still more sensitive to the effects of DFP on the criterion variables upon which selection was based: core body temperature, body weight and a simple operant response for water reward. The flinders S-line were also more sensitive to the effects of DFP on locomotor activity, FR5 responding for a water reward, and analgesia, indicating some degree of generalization. However, diarrhea, a symptom of peripheral effects of DFP, occurred at a similar incidence in the two lines, although males of both lines had higher incidences than the females. Neither of the two lines was affected by DFP for variables in which aversive (i.e. shock) motivation was used: The number of discriminative escape responses and the escape times were similar. These findings indicate that while the effects of DFP do generalize beyond the criterion variables upon which selection was based, the generalization is relatively specific. The data are consistent with the hypothesis that the changes in sensitivity have arisen because of changes in the functioning of a central cholinergic system(s).

Animals↗

Development and disappearance of subsensitivity to pilocarpine following a single administration of the irreversible anticholinesterase angent, DFP.

The present study examined the possibility that subsensitivity to pilocarpine might occur following a single injection of the irreversible anticholinesterase agent, DFP. In one experiment male Sprague-Dawley rats were trained to drink from experimental drinking chambers for 1/2 h per day. After establishment of baselines, pilocarpine hydrochloride (8 mg/kg) was injected i.p. 5 min before the drinking session. One week later DFP or the arachis oil vehicle (1 mg/kg) was injected intramuscularly and injections of pilocarpine were given at varying times thereafter. The suppression of water intake by this dose of pilocarpine was unaffected by pretreatment with arachis oil, but was markedly attenuated by pretreatment with DFP. This subsensitivity was first observed on the second day but had largely disappeared by the 14th day. DFP was found to have comparable effects on water intake and brain acetylcholinesterase activity when the injections were separated by 20 days. In a second experiment the hypothermic effects of pilocarpine were found to be reduced in rats acutely treated with DFP. These data establish that subsensitivity to pilocarpine occurs following a single administration of DFP. This subsensitivity could reflect a reduced sensitivity of postsynaptic receptors to acetylcholine, which may partially account for the behavioural recovery of the rats while acetylcholinesterase activity is still markedly depressed.

Acetylcholinesterase↗