Conditioned place preference associated with level of palmitoylation of PSD-95 in rat hippocampus and nucleus accumbens

Psychostimulant-mediated synaptic plasticity in the hippocampus and nucleus accumbens is one of the pathological features of addiction, a disease of learning and memory. Dynamic palmitoylation of PSD-95 modulates synaptic plasticity, but its role in addiction is not fully understood. Using a morphine-conditioned place preference (CPP) rat model and Acyl-biotin exchange (ABE) labeling we found a correlation between CPP and levels of palmitoylated PSD-95 in the hippocampus and nucleus accumbens. Rats that developed significant CPP had higher levels of palmitoylation of PSD-95 in the hippocampus and nucleus accumbens. Furthermore, palmitoylation of PSD-95 was significantly decreased in the hippocampus but increased in the nucleus accumbens during the beginning of withdrawal. With long-term withdrawal, palmitoylated PSD-95 in these regions recovered, while CPP waned and physical signs gradually disappeared. However, morphine reinjection restored strong CPP without producing any significant changes in palmitoylation of PSD-95. Our findings suggest that CPP is correlated with the dynamics of PSD-95 palmitoylation in rat hippocampus and nucleus accumbens, and could be one of the mechanisms for morphine-dependent synaptic plasticity.