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The Journal of Neuroscience, July 14, 2004, 24(28):6362-6370; doi:10.1523/JNEUROSCI.1205-04.2004

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Behavioral/Systems/Cognitive
The Rate of Cocaine Administration Alters Gene Regulation and Behavioral Plasticity: Implications for Addiction

Anne-Noël Samaha,¹ Nicolas Mallet,² Susan M. Ferguson,¹ François Gonon,² and Terry E. Robinson¹

¹Department of Psychology (Biopsychology Program), University of Michigan, Ann Arbor, Michigan 48109-1109, and ²Centre National de la Recherche Scientifique Unité Mixte de Recherche 5541, Université Victor Segalen, 33077 Bordeaux, France

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.

Key words: psychomotor sensitization; intravenous; rate of infusion; immediate early gene; dopamine reuptake-inhibition; rat

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Received March 31, 2004; revised June 1, 2004; accepted June 1, 2004.

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