The rate of cocaine administration alters gene regulation and behavioral plasticity: implications for addiction.
The rapid delivery of drugs of abuse to the brain is thought to promote addiction, but why this occurs is unknown. In the present study, we characterized the influence of rate of intravenous cocaine infusion (5-100 sec) on three effects thought to contribute to its addiction liability: its ability to block dopamine (DA) uptake, to activate immediate early gene expression, and to produce psychomotor sensitization. Rapid infusions potentiated the ability of cocaine to block DA reuptake, to induce c-fos and arc mRNA expression, especially in mesocorticolimbic regions, and to produce psychomotor sensitization. Thus, the rate at which cocaine is delivered influences both its neurobiological impact and its ability to induce a form of drug experience-dependent plasticity implicated in addiction. We propose that rapidly delivered cocaine may be more addictive, in part, because this more readily induces forms of neurobehavioral plasticity that lead to the compulsive pursuit of drugs.
Samaha
Anne-Noël
AN
Department of Psychology (Biopsychology Program), University of Michigan, Ann Arbor, Michigan 48109-1109, USA.
Mallet
Nicolas
N
Ferguson
Susan M
SM
Gonon
François
F
Robinson
Terry E
TE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D019970:Cocaine-Related Disorders / Q000209:etiology*; D003598:Cytoskeletal Proteins; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D004334:Drug Administration Schedule; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics; D017403:In Situ Hybridization; D007262:Infusions, Intravenous; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D003598:Cytoskeletal Proteins; D018765:Dopamine Uptake Inhibitors; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; C092069:activity regulated cytoskeletal-associated protein; D003042:Cocaine; D004298:Dopamine