The impact of acute or intermittent methamphetamine exposure in utero on neurodevelopment and behaviour in the neonatal rat

In pregnant females there are a variety patterns of methamphetamine (MA) use and correspondingly such patterns may lead to different outcomes for the neonate. The severity of neonatal outcomes is related to the frequency and quantity of MA that the foetus is exposed to. There is a paucity of studies investigating different patterns of exposure for pregnant females taking MA, either clinically or in laboratory animals. To date, our previous work has focused on chronic daily exposureto MA during pregnancy or lactation. The present study aims to determine if acute or intermittent MA exposure in utero at a pharmacological dose affects neurodevelopment and behaviour in the rat offspring.

Pregnant Sprague-Dawley dams (n=9-12 dams/group) received MA (3.75mg/kg) or control (distilled water) via oral gavage on a single gestation day (GD21) or on multiple gestation days (GD6&7, 13&14 and 20&21). A range of well-recognised neurodevelopment parameters were examined in the offspring. Data were analysed using Repeated-Measures ANOVA and Two-way ANOVA or Friedman’s ANOVA, Kruskal-Wallis and Chi-Square with relevant post-hoc tests. The level of significance was p<0.05. All experiments were approved by the Animal Care and Research Ethics Committee, National University of Ireland, Galway (12/NOV/07) and in compliance with the European Communities Council directive 86/609.

A significant increase in neonatal mortality was observed in both MA exposure patterns, as were significant impairments in neurodevelopmental parameters including somatic development (e.g. pinna unfolding, eye opening) and behavioural development (e.g. surface righting, inclined plane test, forelimb grip, Table 1).

Table 1: Neonatal developmental parameters.

Data expressed as percentage of pups achieving the endpoint (n=9-12 pups/group). ***p<0.001, **p<0.01.

This study demonstrates that MA, at a pharmacological dose, has a profound effect on neonatal outcome even when taken on a single occasion, albeit close to the end of gestation. If extrapolated to the clinical scenario, this will give cause for concern regarding the risks associated with this drug of abuse on neurodevelopment.