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A sensitizing d‐amphetamine regimen induces long‐lasting spinophilin protein upregulation in the rat striatum and limbic forebrain
Author(s) -
Boikess Steven R.,
Marshall John F.
Publication year - 2008
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2008.06481.x
Subject(s) - striatum , dendritic spine , amphetamine , sensitization , hippocampus , amygdala , neuroscience , forebrain , medicine , neuroplasticity , endocrinology , dopamine , pharmacology , psychology , hippocampal formation , central nervous system
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.