Substance-induced changes in transcription factors can also produce competing effects on reward function.141 For example, repeated substance use activates accumulating levels of ΔFosB, and animals with elevated ΔFosB exhibit exaggerated sensitivity to the rewarding effects of drugs of abuse, leading to the hypothesis that ΔFosB might be a sustained molecular trigger or switch that helps initiate and maintain a state of addiction.141,142 Next-generation sequencing methods have shown that repeated cocaine exposure leads to histone modifications that act in a combinational fashion to create chromatin signatures that strikingly alter pre-mRNA splicing, an effect that is necessary for the expression of cocaine-induced conditioned place preference.143
