METH exposure alters sperm DNA methylation in F0 mice and mPFC transcriptome in male F1 mice.

Rationale: Methamphetamine (METH) exposure has toxicity in sperm epigenetic phenotype and increases the risk for developing addiction in their offspring. However, the underlying transgenerational mechanism remains unclear.

Objectives: The current study aims to investigate the profiles of sperm epigenetic modifications in male METH-exposed mice (F0) and medial prefrontal cortex (mPFC) transcriptome in their male first-generation offspring (F1).

Paternal methamphetamine exposure induces higher sensitivity to methamphetamine in male offspring through driving ADRB1 on CaMKII-positive neurons in mPFC.

Paternal abuse of drugs, such as methamphetamine (METH), elevates the risk of developing addiction in subsequent generations, however, its underlying molecular mechanism remains poorly understood. Male adult mice (F0) were exposed to METH for 30 days, followed by mating with naïve female mice to create the first-generation mice (F1). When growing to adulthood, F1 were subjected to conditioned place preference (CPP) test.

Sex-specific neurobehavioural outcomes and brain stimulation pattern in adult offspring paternally exposed to methamphetamine.

Paternal methamphetamine (METH) exposure results in long-term behavioural deficits in the sub-generations with a sex difference. Here, we aim to investigate the sex-specific neurobehavioural outcomes in the first-generation offspring mice (F1 mice) paternally exposed to METH prior to conception and explore the underlying brain mechanisms. We found that paternal METH exposure increased anxiety-like behaviours and spatial memory deficits only in female F1 mice and caused depression-like behaviours in the offspring without sex-specific differences.

Astrocyte-selective STAT3 knockdown rescues methamphetamine withdrawal-disrupted spatial memory in mice via restoring the astrocytic capacity of glutamate clearance in dCA1.

Methamphetamine (METH) is a common abused drug. METH-triggered glutamate (Glu) levels in dorsal CA1 (dCA1) could partially explain the etiology of METH-caused abnormal memory, but the synaptic mechanism remains unclear. Here, we found that METH withdrawal disrupted spatial memory in mice, accompanied by the increases in Glu levels and postsynaptic neuronal activities at dCA1 synapses.