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45308301.der.pdf
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45308301
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Chlorpromazine HCl and D-Amphetamine sulfate
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69-09-0, 51-63-8
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600006|600091
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Myers, D. (2000) Assessment of the Effects of Amphetamine or Chlorpromazine on the Motor Activity of Young Rats - Positive Control Study: and, Examination of Brains from Untreated 11 Day Old Rats - Background Control Data: Lab Project Number: 98 3891: HLS058/983891. Unpublished study prepared by Huntingdon Life Sciences Ltd. 115 p.
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2000.0
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D-Amphetamine sulfate & Chlorpromazine HCl: As part of a series of studies submitted to demonstrate the proficiency of Huntingdon Life Sciences, Ltd., Suffolk, England to perform neurotoxicology tests on male and female CD strain (Sprague-Dawley origin) rats, motor activity monitoring (MRID 45308301) was assessed in groups of 10 rats/sex/dose. Amphetamine (D-Amphetamine sulfate) (2.0 mg/kg/day), chlorpromazine (chlorpromazine HCl) (10.0 mg/kg/day), or 0.9% saline control vehicle was administered on postnatal days (PNDs) 13, 17, and 22 by oral gavage at a volume-dosage of 10 mL/kg, 30-minutes prior to testing. Motor activity was monitored over a 1-hour period. Additional untreated rats (15/sex) were allocated for neuropathology and morphometry on PND 11.
All pups survived until sacrifice. No clinical signs were noted in untreated pups allocated for brain examination on PND 11 or in control pups at any age, except one control male was blue and unconscious with slow respiration immediately after dosing on PND 13, but recovered in approximately 5 minutes. No clinical findings were reported for PNDs 13 and 17. On PND 22, Amphetamine-treated pups were overactive after dosing; partially closed eyelids (2 males) and dilated pupils (2 males, 1 female) also were noted. Chlorpromazine-treated pups were underactive after dosing on PND 22. Slow respiration (9 males, 8 females), closed or partially closed eyelids (all pups) and piloerection and/ or hunched posture (4 males, 1 female) were noted.
Absolute body weight was not significantly affected by treatment in either group. Body weight gain was satisfactory and comparable prior to initial dosing on PND 13. Amphetamine did not affect body weight gain, but chlorpromazine was associated with slightly lower weight gain during PNDs 13-17 compared with controls (86% and 76% of controls in males and females, respectively).
Treatment with amphetamine resulted in markedly increased levels of motor activity in males and females on PNDs 13, 17, and 22 throughout the 1-hour recording period. Total low beam activity on each testing day in the treated groups was 308-807% of controls in males and 267-472% of controls in females. Rearing activity was also increased to 143-979% of controls in males and 594-705% of controls in females.
Chlorpromazine-treated pups had slightly reduced motor activity levels on PNDs 13, 17 and 22. Although the magnitude of change was not great, slightly reduced scores were generally evident throughout the 1-hour testing period. Total low beam activity on each testing day for the treated groups was 52-70% of controls in males and 24-58% of controls in females. Rearing activity was also decreased to 15-27% of controls in males and 8-18% of controls in females on PNDs 17 and 22. No rearing was measured in treated males and females on PND 13.
Background control data on brain length, width and weight, and microscopic appearance and morphometry of the brain of PND 11 rats were also generated in this study. For this purpose, 15 rats/sex were killed on PND 11 and subjected to macroscopic necropsy examination. In addition, the brain was weighed and the length and width determined, prior to fixation in 10% neutral buffered formalin. Subsequently, the brains were examined microscopically and morphometric measurements made, recording the thickness of the major layers within the neocortex, hippocampus and cerebellum.
This study is classified as Acceptable/Nonguideline. Huntingdon Life Sciences, Ltd. has demonstrated proficiency in this study for detecting changes in motor due to amphetamine (D-Amphetamine sulfate) and chlorpromazine (chlorpromazine HCl) treatments in Pre and Postweaning (PND 13-22) CD (Sprague Dawley origin) rats for the time period around 1998 (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 [81-9, Developmental neurotoxicity (use 870.3650 or 870.6300 instead of this)]
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Oral
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No Duration Period; Motor activity positive control data
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53777.0
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2012-03-20
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2016-09-07
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Added by
Madison Feshuk
on Apr 25, 2022
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