Distinct proteomic profiles of amphetamine self-administration transitional states.
In the rat, continuous access to d-amphetamine (d-AMPH) leads to lengthy bouts of self-administration, voluntary abstinence, and relapse to self-administration. Previous studies have revealed that the progression from psychostimulant self-administration to abstinence to relapse is mediated in part by the ventral hippocampus. Stimulation of the ventral subiculum (vSub) during voluntary abstinence from d-AMPH self-administration reinstates self-administration and increases nucleus accumbens (NAc) dopamine efflux. Quantitative proteomic examination of the hippocampus from rats naive to amphetamine, during a self-administration session 'Binge', during voluntarily abstinence 'Abstinent', and after reinstatement of self-administration 'Relapse', revealed a differential proteomic state during abstinence. Actin- and cytoskeletal-related proteins were over-represented in the changes occurring during abstinence and suggest a decrease in actin filament polymerization. These changes may underlie alterations in neuronal tone during abstinence that could affect both neurotransmission and behavior. These data provide the first classification of addiction-related behaviors based on clustering of quantitative proteomic measurements. .
Freeman
W M
WM
Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA. wfreeman@psu.edu
Brebner
K
K
Amara
S G
SG
Reed
M S
MS
Pohl
J
J
Phillips
A G
AG
D000199:Actins / Q000378:metabolism; D019969:Amphetamine-Related Disorders / Q000235:genetics* / Q000523:psychology; D000818:Animals; D000697:Central Nervous System Stimulants; D016000:Cluster Analysis; D003627:Data Interpretation, Statistical; D003913:Dextroamphetamine; D004591:Electrophoresis, Polyacrylamide Gel; D005456:Fluorescent Dyes; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology; D007525:Isoelectric Focusing; D008297:Male; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012646:Self Administration; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000199:Actins; D000697:Central Nervous System Stimulants; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D011506:Proteins; D003913:Dextroamphetamine