Acute effects of oral pyridostigmine bromide on conditioned operant performance in rats

Shih, Jiaw-Horn; Liu, Wu-Fu; Lee, Shu-Fen; Lee, Jeng Dong; Ma, Chong; Lin, Chun-Hus

doi:10.1016/0091-3057(91)90012-q

Cited by 18 publications

(7 citation statements)

References 14 publications

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“…Possible cognitive effects of the three treatments will be tested at later stages of this project by two other learning paradigms, conditioned avoidance response, and Morris water maze. Learning impairments have been previously described in rats re- jpet.aspetjournals.org ceiving PB (Shih et al, 1991;Liu, 1992). However, the doses used were considerably higher (6 to 24 mg/kg as a single oral dose) than the one reported in this study (10 mg/kg/day), equivalent, on the basis of body surface area conversion between species, to that taken by soldiers as prophylactic treatment against nerve agent poisoning (1.29 mg/kg/day).…”

Section: Discussionmentioning

confidence: 99%

Delayed Neurologic and Behavioral Effects of Subtoxic Doses of Cholinesterase Inhibitors

Scremin¹,

Shih²,

Huynh³

et al. 2002

J Pharmacol Exp Ther

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We tested the hypothesis that pyridostigmine bromide (PB) intake and/or low-level sarin exposure, suggested by some as causes of the symptoms experienced by Persian Gulf War veterans, induce neurobehavioral dysfunction that outlasts their effects on cholinesterase. Adult male Sprague-Dawley rats were treated during 3 weeks with s.c. saline, PB in drinking water (80 mg/l), sarin (62.5 g/kg; 0.5ϫ LD 50 , three times/week s.c.), or PB in drinking water ϩ sarin. Animals were tested for passive avoidance, nociceptive threshold, acoustic startle, and open field activity 2, 4, or 16 weeks after treatment. Two weeks after sarin, acoustic startle was enhanced, whereas distance explored in the open field decreased. These effects were absent with PB ϩ sarin or PB by itself. No effect on any variable was found at 4 weeks, whereas at 16 weeks sarin induced a decrease and PB ϩ sarin induced an increase in habituation in the open field test. Nociceptive threshold was elevated in the PB ϩ sarin group at 16 weeks. No effect of treatment on passive avoidance was noted in any group. Brain regional acetylcholinesterase and cholineacetyltransferase activities were not affected at any time after treatment, but muscarinic receptors were down-regulated in hippocampus, caudate putamen, and mesencephalon in the sarin group at 2 weeks. In conclusion, this study gives further support to the use of PB against nerve agent poisoning and does not support the hypothesis that delayed symptoms experienced by Persian Gulf War veterans could be due to PB, alone or in association with low-level sarin exposure.

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Section: Discussionmentioning

confidence: 99%

Delayed Neurologic and Behavioral Effects of Subtoxic Doses of Cholinesterase Inhibitors

Scremin¹,

Shih²,

Huynh³

et al. 2002

J Pharmacol Exp Ther

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“…Examples of this can be seen in an operant assessment using a fixed-ratio schedule to detect intoxication after orally ingested pyridostigmine bromide [60] and perchloroethylene [61]. Both studies showed clear intoxication following oral ingestion of the poison, but the latency to intoxication was faster following perchloroethylene ingestion.…”

Section: Discussionmentioning

confidence: 99%

Behavioral intoxication following voluntary oral ingestion of tetramethylenedisulfotetramine: Dose-dependent onset, severity, survival, and recovery

et al. 2017

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Tetramethylenedisulfotetramine (tetramine, or TETS) is a highly toxic rodenticide that has been responsible for over 14,000 accidental and intentional poisonings worldwide. Although the vast majority of TETS poisonings involved tainted food or drink, the laboratory in vivo studies of TETS intoxication used intraperitoneal injection or gavage for TETS exposure. Seeking to develop and characterize a more realistic model of TETS intoxication in the present study, rats were trained to rapidly and voluntarily consume a poisoned food morsel. Initially, the overt toxic effects of TETS consumption across a large range of doses were characterized, then a focused range of doses was selected for more intensive behavioral evaluation (in operant test chambers providing a variable-interval schedule of food reinforcement). The onset of intoxication following voluntary oral consumption of TETS was rapid, and clear dose-dependent response-rate suppression was observed across multiple performance measures within the operant-chamber environment. At most doses, recovery of operant performance did not occur within 30 hours. Food consumption and body weight changes were also dose dependent and corroborated the behavioral measures of intoxication. This voluntary oral-poisoning method with concomitant operant-behavioral assessment shows promise for future studies of TETS (and other toxic chemicals of interest) and may be extremely valuable in characterizing treatment outcomes.

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“…Orally administered PB decreases rates of response in conditioned operant behavior in rats at doses insufficient to cause overt cholinergic crisis, but the lowest effective dose for performance disruption was 6 mg/kg, far higher than the PB pretreatment dose in humans (Shih et al 1991). Evidence exists that at low doses in rats decrements in discrimination involve motivational dysfunction rather than motor impairment (Liu 1992).…”

Section: Adverse Effects In Healthy Subjectsmentioning

confidence: 99%

Clinical Considerations in the Use of Pyridostigmine Bromide as Pretreatment for Nerve-Agent Exposure

Madsen¹,

Hurst²,

MacIntosh³

et al. 2003

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Acute effects of oral pyridostigmine bromide on conditioned operant performance in rats

Cited by 18 publications

References 14 publications

Delayed Neurologic and Behavioral Effects of Subtoxic Doses of Cholinesterase Inhibitors

Delayed Neurologic and Behavioral Effects of Subtoxic Doses of Cholinesterase Inhibitors

Behavioral intoxication following voluntary oral ingestion of tetramethylenedisulfotetramine: Dose-dependent onset, severity, survival, and recovery

Clinical Considerations in the Use of Pyridostigmine Bromide as Pretreatment for Nerve-Agent Exposure

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