1. ¹Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA
2. ²Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
3. ³Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
4. ⁴Microchemical & Proteomics Facility, Emory University School of Medicine, Atlanta GA, USA

Correspondence: WM Freeman, Department of Pharmacology, Penn State College of Medicine, 500 University Drive, H078, PO Box 850, Hershey, PA 17033, USA. Tel: 717 531 0003 ext.280248 Fax: 717 531 5013 E-mail: wfreeman@psu.edu

Received 17 December 2004; Revised 23 February 2005; Accepted 25 February 2005; Published online 26 April 2005.

Abstract

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 naïve 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.