Prenatal methamphetamine exposure increased addiction vulnerability through neural circuit dysfunction and epigenetic...

Methamphetamine (METH), a type of synthetic drug with effects similar to amphetamines, remains a significant public health concern, particularly among women of childbearing age. Prenatal methamphetamine exposure (PME) has been demonstrated to negatively affect fetal neurodevelopment and increase addiction in exposed individuals. Although there is increasing evidence of transgenerational effects, the molecular mechanisms that mediate addiction vulnerability induced by PME are not yet fully understood. In this comprehensive review, we combine findings from epidemiology and mechanistic studies using animal models to create a more complete picture regarding the mechanisms by which PME changes the neural circuitry, through its effects on the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus. There is an increasing body of research on epigenetics that illustrates a relationship between epigenetic alterations to DNA via methylation, histone modifications, and the dysregulation of non-coding RNAs in neurodevelopmental programming and the eventual treatment outcomes for substance use disorders. Elucidating these neurobiological mechanisms provides critical insights for identifying vulnerable populations, developing targeted interventions, and establishing evidence-based strategies to mitigate addiction risk in PME-affected offspring.