Articles
Behavioral and Immunological Effects of Exogenous Butyrylcholinesterase in Rhesus Monkeys

https://doi.org/10.1016/S0091-3057(98)00183-XGet rights and content

Abstract

Although conventional therapies prevent organophosphate (OP) lethality, laboratory animals exposed to such treatments typically display behavioral incapacitation. Pretreatment with purified exogenous human or equine serum butyrylcholinesterase (Eq-BuChE), conversely, has effectively prevented OP lethality in rats and rhesus monkeys, without producing the adverse side effects associated with conventional treatments. In monkeys, however, using a commercial preparation of Eq-BuChE has been reported to incapacitate responding. In the present study, repeated administration of commercially prepared Eq-BuChE had no systematic effect on behavior in rhesus monkeys as measured by a six-item serial probe recognition task, despite 7- to 18-fold increases in baseline BuChE levels in blood. Antibody production induced by the enzyme was slight after the first injection and more pronounced following the second injection. The lack of behavioral effects, the relatively long in vivo half-life, and the previously demonstrated efficacy of BuChE as a biological scavenger for highly toxic OPs make BuChE potentially more effective than current treatment regimens for OP toxicity.

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Subjects

Four experimentally naive male rhesus monkeys (Macaca mulatta), weighing between 8.9–9.4 kg at the time of the study, served as subjects. Three of the monkeys were 7 years of age at the beginning of the study and were obtained from Charles River (Wilmington, MA). One monkey was obtained from the Uniformed Services University of the Health Sciences (Bethesda, MD) and was 16 years old at the beginning of the study. The monkeys were individually housed in stainless steel cages (61 cm W × 71 cm D ×

Behavioral Performance

Unless otherwise indicated, the enzyme injection did not cause any significant effects on behavioral measures (all ps > 0.05). Administration of 27,000 IU Eq-BuChE caused no observable effect on the monkeys’ SPR performance overall or as a function of serial list position. Overall performance remained above 80% correct both before and after injection, as seen in Fig. 1A. A one-way repeated measures ANOVA did not reveal a significant main effect of days, F(4, 12) = 1.241. Figure 1B illustrates

Discussion

The SPR task generated well-controlled responding in all subjects, with high accuracy on both matching and nonmatching trials, and stable, moderate latencies. Accuracy as a function of serial position increased slightly with items later in the list, but was clearly above chance levels at all list positions. This performance is characteristic of rhesus monkeys under similar SPR procedures (13).

Administration of 27,000 and 54,000 IU of Eq-BuChE did not cause any observable gross behavioral

Acknowledgements

The opinions and assertions contained here are the private views of the authors and are not to be construed as official or as reflecting the views of the Army or the Department of Defense. Throughout the study, the monkeys were maintained in compliance with the National Research Council’s Guide for the Care and Use of Laboratory Animals (National Academy Press, 1996). The authors wish to thank B. P. Doctor and David Lenz for their contributing comments to the manuscript.

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