Neuron subtype-specific molecular profiling and gene editing in a mouse model of cocaine addiction

Addiction is a complex and devastating disease that hijacks homeostatic reward signaling, resulting in progressive loss of control over drug consumption and aversive withdrawal symptoms following prolonged abstinence. Recent studies have suggested that epigenetic modifications, particularly DNA methylation and histone methylation, regulate the long-term storage and maintenance of memory, and that defects of certain epigenetic factors affect drug-induced behaviors. We therefore hypothesize that epigenetic modifications in midbrain dopamine (DA) neurons play essential roles in regulating behavioral responses to drugs of abuse. However, cell heterogeneity in brain still represents a technical hurdle that impedes molecular profiling and editing at neuronsubtype resolution.