Operant psychostimulant self-administration in a rat model of depression

• Type of Material: Article
• Authors: Sharon J. Lin, Emory University; S. Alisha Epps, Emory University; Charles H. West, Emory University; Katherine A. Boss-Williams, Emory University; Jay M Weiss, Emory University; David Weinshenker, Emory University
• Language: English
• Date: 2012-12-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.pbb.2012.09.008
• Title of Journal or Parent Work: Pharmacology Biochemistry and Behavior
• ISSN: 0091-3057
• Volume: 103
• Issue: 2
• Start Page: 380
• End Page: 385
• Grant/Funding Information: This work was supported by an Emory SURE Fellowship (to SJL), the National Institute of Neurological Disease and Stroke (NS065663 to SAE), and the National Institute of Drug Abuse (DA027535 to DW).
• Keywords: SEEKING; Behavioral Sciences; DOPAMINERGIC DRUGS; SWIM-TEST; Self-administration; Cocaine; Pharmacology & Pharmacy; Neurosciences & Neurology; COMORBIDITY; REINSTATEMENT; NUCLEUS-ACCUMBENS; Amphetamine; Depression; Science & Technology; Life Sciences & Biomedicine; Rat; COCAINE; Neurosciences; DEPENDENCE; ABUSE; Addiction; DISORDERS
• Research Categories: Biology, Neuroscience; Biology, Genetics; Psychology, Behavioral

Abstract

Depression and psychostimulant addiction are co-morbid conditions; depression is a significant risk factor for psychostimulant abuse, and the rate of depression in drug addicts is higher than in the general population. Despite the prevalence of this comorbidity, there are few animal models examining psychostimulant abuse behaviors in depression. We have shown previously that while rats selectively bred for depression-like phenotypes (SwLo) have blunted mesolimbic dopamine (DA) signaling and locomotor responses to dopaminergic drugs, they voluntarily administer excessive amounts of psychostimulants compared to normal or depression-resistant (SwHi) rats in oral consumption paradigms. To determine whether this increased drug intake by depression-sensitive rats extends to operant self-administration, we assessed fixed ratio-1, progressive ratio, extinction, and reinstatement responding for cocaine and amphetamine in SwLo and SwHi rats. Contrary to the oral consumption results, we found that the SwHi rats generally responded more for both cocaine and amphetamine than the SwLo rats in several instances, most notably in the progressive ratio and reinstatement tests. Food-primed reinstatement of food seeking was also elevated in SwHi rats. These results provide further insight into the neurobiology of depression and addiction comorbidity and caution that oral and operant psychostimulant self-administration paradigms can yield different, and this case, opposite results.