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  • Title: A sensitizing d-amphetamine regimen induces long-lasting spinophilin protein upregulation in the rat striatum and limbic forebrain.
    Author: Boikess SR, Marshall JF.
    Journal: Eur J Neurosci; 2008 Nov; 28(10):2099-107. PubMed ID: 19046390.
    Abstract:
    Structural studies have shown that chronic regimens of psychostimulants increase dendritic spine number in the rat striatum. The present study used Western blotting and radioimmunocytochemistry to examine psychostimulant-induced changes in the levels of spinophilin, a protein found abundantly in dendritic spines. Spinophilin determinations were conducted in striatum as well as several other subcortical regions implicated in psychostimulant-induced neuroplasticity. Rats received an escalating (1-8 mg/kg) dosing regimen of d-amphetamine (twice daily, i.p.) for 5 weeks, were tested for locomotor sensitization, and were killed 28 days later. This amphetamine dosing regimen was found to induce a significant sensitization of locomotor activity in these animals. Using both Western blotting and radioimmunocytochemistry, spinophilin protein was found to be upregulated in the striatum of amphetamine-treated rats. In addition, radioimmunocytochemistry revealed that spinophilin was increased in the septum, hippocampus, amygdala and the cingulate cortex, and was unchanged in sensorimotor cortices. Because it binds to F-actin and protein phosphatase-1, spinophilin has been proposed as a protein linking synaptic transmission to changes in spine morphology. Radioimmunocytochemistry for spinophilin provides a novel approach to identification of brain regions whose neurons undergo dendritic change after chronic exposure to drugs of abuse.
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