Effect of methamphetamine exposure during prenatal and preweaning periods lasts for generations in rats

Abstract

Our previous studies demonstrated that methamphetamine (MA) administration during gestation and/or lactation affects maternal behavior in rats and that birth weight and sensory-motor coordination of their pups are also influenced. The present study tested the hypothesis that the effect of MA induces long-term changes affecting second generation of rats that were not exposed to the drug. Adult females exposed during prenatal and preweaning periods to 5 mg/kg MA daily, were examined for regularity of estrous cycle and mated with stimulus, unexposed males. Dams (nontreated absolute control, saline- and MA-exposed) were observed with their pups in two tests of maternal behavior (observational and retrieval tests). Their pups were further tested throughout the preweaning period to examine their development. Our data demonstrate that MA-exposed mothers displayed more nursing, were more often in the nest and in contact with their pups, and were faster in retrieving their pups than saline-exposed and/or control mothers. There were no differences in litter characteristics, birth weight and weight gain of pups between groups. Interestingly, pups from mothers exposed to MA during prenatal and preweaning period had impaired sensory-motor coordination. They achieved righting reflex in mid-air later than both control groups. Additionally, they had more falls in rotarod and bar-holding tests than pups from both control and saline-exposed mothers. In homing performance, pups from MA- and saline-exposed dams learned slower to return to the home box than pups from control dams. Thus, the present study demonstrates that MA abused by mothers may affect two generations of their offspring.

Motor and cognitive outcomes through three years of age in children exposed to prenatal methamphetamine

“…In rodents, MA is toxic to dopaminergic and serotonergic neurons(42;43) and neurotoxic effects on serotogenetic neurons produce neurochemical alternations in the central nervous system(44;45). Prenatal MA exposure in 3 week old rats (equivalent to approximately age 5 years) demonstrate impaired postural motor movements(46) and these abnormal postural movements can still be noted in the second generation of rats exposed to MA prenatally(47). Administration of MA to laboratory animals also results in delayed motor development(48;49) and in pregnant mice, MA administration to the mother leads to dopaminergic nerve terminal degeneration and long term motor deficits in the exposed offspring(50).…”

Short-term outcomes of mothers and infants exposed to antenatal amphetamines

“…Whether this was due to maternal choice or to advice from care-givers is uncertain as milk amphetamine levels have been shown to be up to seven times higher than maternal plasma 31 32. We have previously demonstrated that breast milk feeds, even without the pacifying effect of suckling, ameliorates the severity of opiate withdrawal33 and further study regarding the interaction between amphetamines and lactation is recommended.…”

Prenatal exposure to drugs: effects on brain development and implications for policy and education

“…Furthermore, alterations in the levels and activity of the noradrenergic and serotonergic systems have been demonstrated in animals exposed to either amphetamine or methamphetamine 78-80. Some of the functional consequences (such as impaired sensory-motor coordination) of prenatal methamphetamine exposure are transmitted to the next generation of offspring 81. These findings demonstrate that prenatal amphetamine or methamphetamine exposure leads to a complex behavioral phenotype with similarly complex molecular and cellular roots.…”