Chronic morphine exposure and its abstinence alters dendritic spine morphology and upregulates Shank1

• Chronic morphine increase dendritic spines in cortex and nucleus accumbens of mice.
• These changes are persistent even after two months of morphine withdrawal.
• Chronic morphine and abstinence also increases Shank1, at protein and mRNA levels.
• In addition, some postsynaptic proteins are persistently elevated upon withdrawal.
• Results suggest Shank1 may regulate dendritic spines during morphine treatment.

Exposure to chronic drugs of abuse has been reported to produce significant changes in postsynaptic protein profile, dendritic spine morphology and synaptic transmission. In the present study we demonstrate alterations in dendritic spine morphology in the frontal cortex and nucleus accumbens of mice following chronic morphine treatment as well as during abstinence for two months. Such alterations were accompanied with significant upregulation of the postsynaptic protein Shank1 in synaptosomal enriched fractions. mRNA levels of Shank1 was also markedly increased during morphine treatment and during withdrawal. Studies of the different postsynaptic proteins at the protein and mRNA levels showed significant alterations in the morphine treated groups compared to that of saline treated controls. Taken together, these observations suggest that Shank1 may have an important role in the regulation of spine morphology induced by chronic morphine leading to addiction.