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Differential Reinforcing Effects of Cocaine and GBR-12909: Biochemical Evidence for Divergent Neuroadaptive Changes in the
 

Summary: Differential Reinforcing Effects of Cocaine and GBR-12909:
Biochemical Evidence for Divergent Neuroadaptive Changes in the
Mesolimbic Dopaminergic System
Srihari R. Tella,1,2 Bruce Ladenheim,3 Anne M. Andrews,4 Steven R. Goldberg,1,2 and Jean Lud Cadet3
1Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20007, 2Behavioral
Pharmacology and Genetics Section and 3Molecular Neuropsychiatry Section, National Institutes of Health/National
Institute on Drug Abuse, Division of Intramural Research, Baltimore, Maryland 21224, and 4Laboratory of Clinical Science,
National Institute of Mental Health, Bethesda, Maryland 20892
The dopamine (DA) transporter is thought to be the primary
mediator of reinforcing effects of cocaine. In the present
study, an intravenous drug self-administration procedure, in
vitro autoradiography, and HPLC methods were used to
investigate possible differences in reinforcing and neuroad-
aptive responses to cocaine versus GBR-12909, a selective
inhibitor of the DA transporter with a postulated therapeutic
use in cocaine abuse. Drug-naive rats readily acquired and
subsequently maintained cocaine self-administration behav-
ior during 2 hr daily sessions over a prolonged period. In
contrast, although GBR-12909 was initially self-
administered, both cocaine-naive and cocaine-trained rats

  

Source: Andrews, Anne M. - Huck Institutes of the Life Sciences, Pennsylvania State University

 

Collections: Biology and Medicine