Methamphetamine exposure during pregnancy: Neurodevelopmental consequences for the offspring

Abstract

Methamphetamine (MA) abuse during pregnancy is a significant concern worldwide. Improving our understanding of the consequences of such exposure on the child is paramount and animal models provide an alternative method of investigating this growing issue. The present work aimed to investigate the developmental, behavioural and neurochemical effects of MA exposure on rat offspring following: 1) prenatal exposure to a range of doses; 2) prenatal and/or postnatal exposure; 3) prenatal intermittent and acute exposure and 4) prenatal exposure via different routes of administration, namely oral (gavage) and subcutaneous (sc). Prenatal and postnatal chronic exposure to MA leads to lower body weight gain and food intake in the mothers and these effects were transient and dose-dependent. Maternal care was compromised by MA when given prenatally by sc injection. Neonatal death was most significant after intermittent and acute prenatal exposure to MA and also after chronic exposure prenatally and postnatally. Chronic MA exposure prenatally and/or postnatally resulted in somatic developmental delays in pinna unfolding, fur appearance and eye opening, effects that were more pronounced following sc administration. Somatic development parameters such as ano-genital distance and body length were only altered by low dose MA or MA sc exposure. Behavioural impairments in surface righting, inclined plane and forelimb grip were only noted after chronic MA exposure prenatally and/or postnatally. All behavioural deficits observed were greater in the MA sc-exposed offspring. In adulthood, prenatal chronic exposure to MA lead to decreased anxiety-like behaviour and increased depressive-like behaviour in the elevated plus maze and forced swim test, respectively. Our neurochemical results showed that parturition and/or lactation and age increased oxidative stress compared to non-pregnant females however, prenatal or postnatal MA had no significant effect on oxidative stress in the mothers or offspring. In conclusion, this research shows that MA exposure during pregnancy and lactation can lead to long-term developmental deficits in offspring. This developmental profile may offer guidance clinically as to what might be expected when a mother abuses this drug during pregnancy or lactation.