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Published on: January 22, 2016
Prolonged methamphetamine exposure during a critical period in neonatal Sprague Dawley rats does not exacerbate
Michael T Williams1,2, Robyn M Amos-Kroohs1,2, Charles V Vorhees1,2
1Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Insights
Methamphetamine (MA) exposure during sensitive developmental periods in rats causes cognitive deficits. Extending this exposure did not worsen learning and memory impairments in young rats.
Area of Science:
- Neuroscience
- Developmental Psychology
- Toxicology
Background:
- Prenatal methamphetamine (MA) exposure is linked to cognitive deficits in children.
- Early postnatal MA exposure in rats also causes cognitive impairments.
Purpose of the Study:
- To investigate if extending MA administration during early postnatal development exacerbates cognitive deficits.
- To compare allocentric and egocentric learning deficits following different MA exposure durations.
Main Methods:
- Rat pups (Sprague Dawley) received MA (10 mg/kg) or saline from postnatal days (P)6-20.
- Exposure groups included MA6-20, MA6-15, and MA11-20.
- Cognitive function was assessed using Morris water maze (allocentric) and Cincinnati water maze (egocentric) tests starting on P60.
Main Results:
- All MA-exposed groups showed allocentric deficits.
- MA6-15 and MA6-20 groups exhibited egocentric deficits.
- Extended MA exposure (MA6-15, MA6-20) resulted in similar, significant learning and memory deficits compared to shorter exposure (MA11-20).
- No significant differences in conditioned freezing were observed across groups.
Conclusions:
- Early postnatal MA exposure induces significant allocentric and egocentric learning deficits.
- Extending MA exposure beyond critical developmental windows (P6-15, P11-20) did not worsen these cognitive impairments.
- Learning deficits were sex-dependent, but MA did not interact with sex.
Abstract:
Children exposed to methamphetamine (MA) in utero have cognitive deficits. MA administration in rats for 5-10 days between postnatal days (P)6 and 20 produces cognitive deficits. The purpose of this study was to determine if extending MA administration by 5 days within P6-20 would exacerbate allocentric (Morris water maze) and egocentric (Cincinnati water maze) learning deficits. Sprague Dawley female and male offspring (split-litter design) were administered saline (SAL) or MA (10 mg/kg) four times daily from P6 to 20 to create four groups: (a) SAL from P6 to 20, (b) MA from P6 to 20 (MA6-20), (c) MA from P6 to 15 (MA6-15), or (d) MA from P11 to 20 (MA11-20); the latter groups received saline on days they did not receive MA. Egocentric, allocentric, and conditioned freezing tests began on P60. The MA6-15 and MA6-20 groups showed egocentric deficits, all MA groups had allocentric deficits but no differences in conditioned freezing compared with SAL controls. The MA6-15 and MA6-20 groups had similar deficits in learning and memory that were larger than in the MA11-20 group. Learning in both mazes was sex dependent, but no interactions with MA were found. The data demonstrate that extending the exposure period of MA beyond the sensitive periods (P6-15 and P11-20) did not exacerbate the cognitive deficits.
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