Behavioral and growth effects induced by low dose methamphetamine administration during the neonatal period in rats.
The investigation of methamphetamine exposure during neonatal development in rats has demonstrated that long-term spatial learning deficits are induced. A previous dose-response study showed that administration of 5 mg/kg methamphetamine, four times daily from postnatal days 11 to 20 produced these deficits, although the effects were not as severe as at higher doses of 10 or 15 mg/kg. This study examined concentrations of methamphetamine at or below 5mg/kg given over the same period of time. Five different concentrations of methamphetamine (i.e., 5, 2.5, 1.25, 0.625, or 0) were administered every 2 h four times daily from postnatal days 11 to 20. Body weights, zero maze performance, and Morris water maze learning were examined. A dose-dependent decrease in body weight was observed during the period of methamphetamine administration and these lower weights continued throughout adulthood for the 5, 2.5, and 1.25 mg/kg concentrations, although the adult decreases were negligible. No differences were noted in the zero maze. In the Morris water maze during the acquisition period, dose-dependent differences in spatial orientation were seen, however non-dose related deficits were observed for other parameters. During the shifted platform phase ("reversal"), a similar dose-dependent difference in spatial orientation was observed, although no other effects were noted during this phase. Females performed worse than males regardless of treatment or the phase of learning in the Morris water maze. These data suggest that even lower doses of methamphetamine can alter learning and memory in adulthood, although with less consistent results than with doses higher than 5 mg/kg/dose. These data would caution against even casual use of methamphetamine by women during pregnancy since even low doses could alter the ability of the child to learn.
Williams
Michael T
MT
Division of Pediatric Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
Moran
Mary S
MS
Vorhees
Charles V
CV
D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology*; D008568:Memory / Q000187:drug effects* / Q000502:physiology*; D008694:Methamphetamine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000697:Central Nervous System Stimulants; D008694:Methamphetamine