title: A sensitizing d-amphetamine regimen induces long-lasting spinophilin protein upregulation in the rat striatum and limbic forebrain.
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.
authors.affiliation: Department of Neurobiology & Behavior, University of California Irvine, Irvine, CA 92697-4550, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Boikess
authors.forename: John F
authors.initials: JF
authors.lastname: Marshall
mesh_terms: D019969:Amphetamine-Related Disorders / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000187:drug effects* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D013995:Time; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000099273:Neurabins
chemical_list: D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D000099273:Neurabins