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45441303.der.pdf
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45441303
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Scopolamine hydrobromide, (+/-)-8-Hydroxy-2-(di-n-propylamino tetralin hydrobromide, and Piperazine, 1-(3-chlorophenyl)-, hydrochloride
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114-49-8|87394-87-4|87394-87-4
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600094|600095|600096
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Sheets, L. (2001) Historical Control and Method Validation Studies for A Developmental Neurotoxicity Screening Battery Auditory Startle Habituation and Cognitive Function: Passive Avoidance and Water Maze Conditioning: Lab Project Number: 98-992-VV: 98- 992-UM: 98-992-WC. Unpublished study prepared by Bayer Corporation. 191 p. {OPPTS 870.6300}
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2001.0
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Four separate studies (MRID 45441303) were conducted on Wistar (Crl:WI(HAN)BR rats to refine and validate auditory startle habituation, water maze conditioning, and passive avoidance conditioning test procedures for use in a developmental neurotoxicity screening battery.
Study 1: (no test material) Auditory startle habituation tests were conducted on three groups of rats (12 rats/sex/group; 8 weeks of age). Each group was tested under identical conditions except the inter-trial interval was 10, 15, or 20 seconds. Both sexes of all three groups exhibited habituation. The magnitude of habituation did not vary with the inter-trial interval in either sex, and there were no gender-related differences in the measured reflexes. The study demonstrated that the test system is adequate to measure startle reflex response and habituation, and that any of the three inter-trial intervals is suitable for this test procedure.
Study 2: Auditory startle habituation tests were conducted in a series of three experiments on groups of rats from the litters of untreated dams. Experiment 1 (no test material) had three groups of weanling rats that were tested on PND 22 under identical conditions except the inter-trial interval was 10, 15, or 20 seconds. Both sexes of all three groups exhibited habituation with no discernible differences. Experiment 2 used the males from Experiment 1 at 30 days of age, which included groups given reference compounds known to affect the reflex response [(subcutaneous (sc) injections of 80HDPAT, 0.25 mg/kg; intraperitoneal (ip) injections of mCPP (5 mg/kg)]. The testing demonstrated the respective decreased and increased responses anticipated from the compounds, but not to an extent that was statistically significant. Experiment 3 was conducted on groups of female rats at 32 days of age using two dose levels of 80HDPAT (0.5 or 1.0 mg/kg sc). A dose-related response was demonstrated in the treated groups with the higher dose level causing a statistically significant (p<0.05) increased response amplitude when compared to the saline control group.
Study 3: Water maze conditioning tests (M-shaped maze) to evaluate learning were conducted on two groups of rats 8 weeks of age. One group was given a sc injection of scopolamine HBr (1.0 mg/kg). The scopolamine HBr-treated group required 2 to 3 more trials (18 to 22%) to reach the criterion, had more rats that failed to reach criterion (3 males and 5 females versus 1 male and 2 females for controls), and demonstrated an increased time to complete the escape task by 1.5 to 2 seconds (averages were 22-25% higher in males and 27-114% in females). None of these differences was statistically significant.
Study 4: Passive avoidance conditioning tests to evaluate learning were conducted on two groups of male rats 5 weeks of age. One group was given a sc injection of scopolamine HBr (1.0 mg/kg). The scopolamine HBr-treated group required significantly (p<0.05) more trials to reach the criterion. Latency was significantly decreased (p<0.05) in one of two trials in both the acquisition and retention phases of the study, but there was no discernible difference in the other two trials.
This study is classified Acceptable/Nonguideline. Bayer Corporation has demonstrated proficiency in this study for detecting changes in postweaning Wistar Crl:WI(HAN)BR rats in: 1) Auditory Startle (GSD 30-32) due to 80HDPAT and mCPP treatment, and 2) Learning and Memory (water maze (8 weeks) and passive avoidance (5 weeks)) due to Scopolamine HBr in postweaning Wistar Crl:WI(HAN)BR rats for the time period around 1998-1999 (in life period of study). This positive control study does not satisfy any guideline requirement.
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Other
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NA [83-6, Developmental Neurotoxicity]
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Intraperitoneal
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No Duration Period; Also included subcutaneous injections
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54595.0
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2012-03-20
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2016-09-01
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Added by
Madison Feshuk
on Apr 25, 2022
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