Transgenerational Effects of Paternal Methamphetamine Exposure in Mice

<p>  Amphetamine-type stimulants are widely abused worldwide. In Japan, methamphetamine (METH) abuse is particularly high and continues to be the most abused drug. It is reported that maternal METH abuse led to lower birth weight and impaired motor growth. However, despite the fact that most METH abusers are male, the impact of paternal abuse on the next generation is unclear. Therefore, we used a mouse model to examine the effects of paternal METH abuse on the next (F1) and subsequent (F2) generations. </p><p>  Male ICR mice (6-week-old) were administered METH or saline for 21 days and then mated with naïve female mice to obtain F1 mice. Body weight, righting reflex, the cliff avoidance test, and the wire-hanging test were performed to evaluate the growth of pups. Six-week-old F1 mice were subjected to spontaneous locomotor activity (LA) and the elevated plus-maze test, and 7-week-old F1 mice to the passive avoidance test. The striatum and hippocampus samples were collected from 7-week-old F1 mice, and the gene expression levels were measured by qPCR. Nine-week-old male F1 mice were mated with females to obtain F2 mice. F2 mice were tested in the same manner as F1 mice. </p><p>  Both F1 and F2 mice of the METH group showed significant growth retardation compared to the respective control group. LA of both F1 and F2 mice was significantly lower in the METH group than in the control group. In the passive avoidance test, F1 mice of the METH group showed a decrease in memory performance, but F2 mice did not. In the brain of F1 and F2 mice, changes in Comt and Gabra3 expressions were observed. These results suggest that paternal METH abuse may affect certain gene expressions, resulting in developmental delay in the following generations.</p>