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Assessment of a combination of physostigmine and scopolamine as pretreatment against the behavioural effects of organophosphates in the common marmoset (Callithrix jacchus)

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Abstract

Rationale

There is a requirement to ensure that UK armed forces are provided with the best possible medical countermeasures to prevent or mitigate the effects of exposure to nerve agents. When pretreatments are under consideration, it is of particular importance to ensure that they do not in themselves give rise to adverse effects and do not exacerbate the effects of agent exposure.

Objectives

The present study was designed to address these considerations for a combination of physostigmine and scopolamine as a potential pretreatment regimen.

Methods

Common marmosets were trained to perform a two-choice discrimination serial reversal task, and baseline data were collected. Subjects received a dose of either soman or sarin after 2 weeks of pretreatment with either saline or physostigmine and scopolamine via miniosmotic pump.

Results

No effects of physostigmine and scopolamine were seen on task accuracy or response rates. Neither accuracy of reversal performance nor number of responses made were significantly changed by administration of either soman or sarin subsequent to pretreatment with physostigmine/scopolamine. In the groups pretreated with saline, performance of the behavioural task, in terms of responses made, was virtually abolished on the day the OP was administered, but a significant increase in accuracy of performance was seen over the 2- to 14-day period following administration.

Conclusions

A combination of physostigmine and scopolamine, which is known to protect against nerve-agent lethality, offers protection against the effects of soman and sarin on behavioural performance, as measured by a discrimination reversal task. The improved performance observed following nerve agent requires further investigation.

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References

  • Aigner TG, Mitchell SJ, Aggleton JP, DeLong MR, Struble RG, Price DL, Wenk GL, Mishkin M (1987) Effects of scopolamine and physostigmine on recognition memory in monkeys with ibotenic-acid lesions of the nucleus basalis of Meynert. Psychopharmacology 92:292–300

    CAS  PubMed  Google Scholar 

  • Blokland A (1996) Acetylcholine: a neurotransmitter for learning and memory? Brain Res Rev 21:285–300

    Article  Google Scholar 

  • Carey GJ, Costall B, Domeney AM, Gerrard PA, Jones DN, Naylor RJ, Tyers MB (1992) Ondansetron and arecoline prevent scopolamine-induced cognitive deficits in the marmoset. Pharmacol Biochem Behav 42:75–83

    Article  CAS  PubMed  Google Scholar 

  • Cotterman TE, Meyer DR, Wickens DD (1956) Discrimination reversal learning in marmosets. J Comp Physiol Psychol 49:539–541

    Google Scholar 

  • Crofts HS (1998) Methodology for the repeated assessment of cognitive and physiological parameters within a home cage environment in the common marmoset (Callithrix jacchus): assessment of repeated attentional set shifting and the sleep electroencephalogram. Thesis, University of Bristol

  • Crofts HS, Muggleton NG, Pearce PC, Nutt DJ, Scott EAM (1995) A home-cage system for neuropsychological testing in non-human primates. J Psychopharmacol Suppl 9:A12

    Google Scholar 

  • Crofts HS, Muggleton NG, Bowditch AP, Pearce PC, Nutt DJ, Scott EA (1999) Home cage presentation of complex discrimination tasks to marmosets and rhesus monkeys. Lab Anim 33:207–214

    CAS  PubMed  Google Scholar 

  • Dirnhuber P, French MC, Green DM, Leadbeater L, Stratton JA (1979) The protection of primates against soman poisoning by pretreatment with pyridostigmine. J Pharm Pharmacol 31:295–299

    CAS  PubMed  Google Scholar 

  • D'Mello GD, Duffy EA (1985) The acute toxicity of sarin in marmosets (Callithrix jacchus): a behavioral analysis. Fundam Appl Toxicol 5:S169–S174

    CAS  PubMed  Google Scholar 

  • Fosbraey P, Wetherell JR, French MC (1990) Neurotransmitter changes in guinea-pig brain regions following soman intoxication. J Neurochem 54:72–79

    CAS  PubMed  Google Scholar 

  • Harder JA, Baker HF, Ridley RM (1998) The role of the central cholinergic projections in cognition: implications of the effects of scopolamine on discrimination learning by monkeys. Brain Res Bull 45:319–326

    Article  CAS  PubMed  Google Scholar 

  • Harris LW, Talbot BG, Lennox WJ, Anderson DR, Solana RP (1991) Physostigmine (alone and together with adjunct) pretreatment against soman, sarin, tabun and VX intoxication. Drug Chem Toxicol 14:265–281

    CAS  PubMed  Google Scholar 

  • Leadbeater L, Inns RH, Rylands JM (1985) Treatment of poisoning by soman. Fundam Appl Toxicol 5:S225–S231

    CAS  PubMed  Google Scholar 

  • Lennox WJ, Harris LW, Anderson DR, Solana RP, Murrow ML, Wade JV (1992) Successful pretreatment/therapy of soman, sarin and VX intoxication. Drug Chem Toxicol 15:271–283

    CAS  PubMed  Google Scholar 

  • Mackintosh NJ (1962) The effects of overtraining on a reversal and non reversal shift. J Comp Physiol Psychol 55:555–559

    Google Scholar 

  • Mirza NR, Stolerman IP (2000) The role of nicotinic and muscarinic acetylcholine receptors in attention. Psychopharmacology 148:243–250

    CAS  PubMed  Google Scholar 

  • Muir JL (1997) Acetylcholine, aging, and Alzheimer's disease. Pharmacol Biochem Behav 56:687–696

    CAS  PubMed  Google Scholar 

  • Pearce PC, Crofts HS, Muggleton NG, Scott EAM (1998) Concurrent monitoring of EEG and performance in the common marmoset: a methodological approach. Physiol Behav 63:591–599

    Article  CAS  PubMed  Google Scholar 

  • Pearce PC, Crofts HS, Muggleton NG, Ridout D, Scott EAM (1999) The effects of acutely administered low dose sarin on cognitive behaviour and the electroencephalogram in the common marmoset. J Psychopharmacol 13:121–128

    Google Scholar 

  • Ridley RM, Bowes PM, Baker HF, Crow TJ (1984) An involvement of acetylcholine in object discrimination learning and memory in the marmoset. Neuropsychologia 22:253–263

    Article  CAS  PubMed  Google Scholar 

  • Ridley RM, Baker HF, Drewett B, Johnson JA (1985) Effects of ibotenic acid lesions of the basal forebrain on serial reversal learning in marmosets. Psychopharmacology 86:438–443

    CAS  PubMed  Google Scholar 

  • Roberts AC, Robbins TW, Everitt BJ (1988) The effects of intradimensional and extradimensional shifts on visual discrimination learning in humans and non-human primates. Q J Exp Psychol B 40:321–341

    CAS  PubMed  Google Scholar 

  • Roberts AC, Robbins TW, Everitt BJ, Jones GH, Sirkia TE, Wilkinson J, Page K (1990) The effects of excitotoxic lesions of the basal forebrain on the acquisition, retention and serial reversal of visual discriminations in marmosets. Neuroscience 34:311–329

    CAS  PubMed  Google Scholar 

  • Roberts AC, Robbins TW, Everitt BJ, Muir JL (1992) A specific form of cognitive rigidity following excitotoxic lesions of the basal forebrain in marmosets. Neuroscience 47:251–264

    CAS  PubMed  Google Scholar 

  • Robbins TW, McAlonan G, Muir JL, Everitt BJ (1997) Cognitive enhancers in theory and practice: studies of the cholinergic hypothesis of cognitive deficits in Alzheimer's disease. Behav Brain Res 83:15–23

    Google Scholar 

  • Rusted JM, Warburton DM (1988) The effects of scopolamine on working memory in healthy young volunteers. Psychopharmacology 96:145–152

    Google Scholar 

  • Sarter M (1994) Neuronal mechanisms of the attentional dysfunctions in senile dementia and schizophrenia: two sides of the same coin? Psychopharmacology 114:539–550

    CAS  PubMed  Google Scholar 

  • Scott EAM, Hollands RN, Wetherall JR (1994) The current UK medical countermeasures for nerve agent poisoning; physostigmine and hyoscine as an alternative to pyridostigmine. In: Proceedings of the CB Medical Treatment Symposium, AC-Laboratorium Spiez, Switzerland, pp 1.14–1.17

  • Taffe MA, Weed MR, Gold LH (1999) Scopolamine alters rhesus monkey performance on a novel neuropsychological test battery. Cogn Brain Res 8:203–212

    Article  CAS  Google Scholar 

  • von Bredow J, Corcoran K, Maitland G, Kaminskis A, Adams N, Wade J (1991) Efficacy evaluation of physostigmine and anticholinergic adjuncts as a pretreatment for nerve agent intoxication. Fundam Appl Toxicol 17:782–789

    PubMed  Google Scholar 

  • Warburton DM, Brown K (1972) The facilitation of discrimination performance by physostigmine sulphate. Psychopharmacologia 27:275–284

    CAS  PubMed  Google Scholar 

  • Wetherell A (1992) Effects of physostigmine on stimulus encoding in a memory-scanning task. Psychopharmacology 109:198–202

    CAS  PubMed  Google Scholar 

  • Wetherell JR (1994) Continuous administration of low dose rates of physostigmine and hyoscine to guinea-pigs prevents the toxicity and reduces the incapacitation produced by soman poisoning. J Pharm Pharmacol 46:1023–1028

    CAS  PubMed  Google Scholar 

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Acknowledgement

This study was funded by the UK Ministry of Defence.

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Authors and Affiliations

  1. Psychopharmacology Unit, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK

    N. G. Muggleton & H. S. Crofts

  2. DSTL Biomedical Sciences, , Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK

    A. P. Bowditch, E. A. M. Scott & P. C. Pearce

  3. Department of Experimental Psychology, University of Oxford, South Parks Road, Oxford, OX1 3UD, UK

    N. G. Muggleton

  4. Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK

    H. S. Crofts

Authors
  1. N. G. Muggleton
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  2. A. P. Bowditch
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  3. H. S. Crofts
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  4. E. A. M. Scott
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  5. P. C. Pearce
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Correspondence to N. G. Muggleton.

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Muggleton, N.G., Bowditch, A.P., Crofts, H.S. et al. Assessment of a combination of physostigmine and scopolamine as pretreatment against the behavioural effects of organophosphates in the common marmoset (Callithrix jacchus). Psychopharmacology 166, 212–220 (2003). https://doi.org/10.1007/s00213-002-1324-7

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  • DOI: https://doi.org/10.1007/s00213-002-1324-7

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