The consequences of prenatal or postnatal methamphetamine exposure on neonatal development in rat offspring

K McDonnell-Dowling1,2, J P Kelly1,2. 1Discipline of Pharmacology and Therapeutics, NUI, Galway, Galway, Ireland, 2Galway Neuroscience Centre, National Centre for Biomedical Engineering Science, NUI, Galway, Galway, Ireland

In recent years, there has been an increase in the number of preclinical studies investigating prenatal and postnatal methamphetamine (MA) exposure due to growing concerns about MA use during pregnancy and/or lactation in humans (1). For such studies, it is important to represent the human scenario as closely as possible, but to date most preclinical studies have deviated from this regarding dose, route of administration and exposure durations. The aim of this study was to determine if prenatal or postnatal MA exposure at a pharmacological dose affects neurodevelopment in the rat offspring.

Pregnant Sprague-Dawley dams (n=8-10 dams/group) received MA (3.75mg/kg) or control (distilled water, VEH) daily via oral gavage from gestation day 7-21 or postnatal day (PND) 1-21. 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 and Kruskal-Wallis with relevant post-hoc tests. The level of significance was p<0.05.

Prenatal and postnatal MA significantly reduced maternal weight gain, which is correlated to reduced food intake in the prenatal and postnatal periods, respectively. A significant increase in pup mortality (stillborn and neonatal) was observed in both MA treatment groups. Significant impairments in neurodevelopmental parameters were also evident in both MA treatment groups including somatic development (e.g. fur appearance, pinna unfolding) and behavioural development (e.g. surface righting, forelimb grip, Table 1).

Table 1: Neonatal developmental parameters. Data expressed as percentage of pups achieving the endpoint. ***p<0.001, **p<0.01, *p<0.05.

This study demonstrates that MA, at a pharmacological dose, can have a profound effect on neonatal outcome when administered prenatally or postnatally. If extrapolated to the clinical scenario, this will give cause for concern regarding the risks associated with this drug of abuse on neonatal neurodevelopment.

(1) National Advisory Committee on Drugs (NACD) & Public Health Information and Research Branch (PHIRB) 2008, Ballsbridge, Dublin 4 & Stormont, Belfast.