4.5 Article

Phasic inhibition of dopamine uptake in nucleus accumbens induced by intravenous cocaine in freely behaving rats

期刊

NEUROSCIENCE
卷 98, 期 4, 页码 729-741

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0306-4522(00)00168-8

关键词

cocaine self-administration; dopamine uptake; voltammetry; reward (euphoria); addictive behavior

资金

  1. NATIONAL INSTITUTE ON DRUG ABUSE [K01DA000335, R01DA002451] Funding Source: NIH RePORTER
  2. NIDA NIH HHS [DA 02451, DA 00335] Funding Source: Medline

向作者/读者索取更多资源

A new approach combining fast-scan cyclic voltammetry with iontophoretic dopamine delivery was used in freely behaving rats to evaluate the time-course of dopamine uptake inhibition in nucleus accumbens induced by intravenous cocaine at a dose (1.0 mg/kg) known to maintain self-administration behavior. Cocaine significantly increased the decay time of the dopamine response without altering its magnitude or time to peak. An increase in decay time was evident at 2 min, peaked at 6 min (+ 87%), and decreased to baseline at 18 min after a single cocaine injection. The change in decay time was similar in all rats and remained essentially the same, albeit slightly larger, for subsequent cocaine injections both within a session and over repeated sessions. The change in dopamine decay time did not correlate with cocaine-induced motor activation, which was maximal during the first minute after injection and decreased slowly over the next 20 min. Our data provide direct evidence for a phasic change in dopamine uptake induced by intravenous cocaine under behaviorally relevant conditions. The relatively slow and gradual development of dopamine uptake inhibition, which peaks at times when behaving rats self-inject cocaine, is inconsistent with the suggested role of this mechanism in the acute rewarding (euphoric) effects of self-injected cocaine, but supports its role in the activational and motivational aspects of drug-seeking and drug-taking behavior. Because intravenous cocaine enters the brain rapidly and peaks in neural tissue (1-2 min) long before it effectively inhibits dopamine uptake (6 min), it appears that some of the acute psychoemotional (rush), behavioral, autonomic, and neuronal effects of this drug, which are apparently resistant to dopamine receptor blockade, are mediated via rapid central or peripheral mechanisms independent of monoamine uptake. Published by Elsevier Science Ltd.

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