Regardless of the nature of the illicit drug abused, there was a strong positive correlation between GluA1 and PSD-95 mRNA expression levels that was not observed in control subjects. Similarly, correlation structure analysis of the network of proteins related to glutamatergic neurotransmission revealed that the GluA1—PSD-95 relationship specifically distinguished heroin abusers from controls. These findings are intriguing given that PSD-95 induces GluA1 delivery into synapses, which is coupled to the strengthening of excitatory synapses during experience-driven learning (6). In addition, trafficking of GluA1 into the active synaptic site is consistently observed in relation to drug-seeking behavior in animal models (33–36).
