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      Cocaine increases medial prefrontal cortical glutamate overflow in cocaine-sensitized rats: a time course study.

      1 ,
      The European journal of neuroscience
      Wiley

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          Abstract

          Excitatory amino acid transmission within mesocorticolimbic brain pathways is thought to play an important role in behavioural sensitization to psychomotor stimulants. The current studies evaluated a time course of the effects of cocaine on extracellular glutamate levels within the medial prefrontal cortex (mPFC) following increasing periods of withdrawal from repeated cocaine exposure. Male Sprague-Dawley rats underwent stereotaxic surgeries and were pretreated daily with saline (1 mL/kg/day x 4 days, i.p.) or cocaine (15 mg/kg/day x 4 days, i.p.) and withdrawn for 1, 7 or 30 days. After withdrawal rats were challenged with the same dose of saline or cocaine and in vivo microdialysis of the mPFC was conducted with concurrent analysis of locomotor activity. Animals that were withdrawn from repeated daily cocaine for 1 day and 7 days displayed an augmentation in cocaine-induced mPFC glutamate levels compared to saline and acute control subjects, which were similarly unaffected by cocaine challenge. At the 7 day time point, a subset of animals that received repeated cocaine did not express behavioural sensitization, nor did these animals exhibit the enhancement in mPFC glutamate in response to cocaine challenge. In contrast to these early effects, 30 days of withdrawal resulted in no significant changes in cocaine-induced mPFC glutamate levels regardless of the pretreatment or behavioural response. These data suggest that repeated cocaine administration transiently increases cocaine-induced glutamate levels in the mPFC during the first week of withdrawal, which may play an important role in the development of behavioural sensitization to cocaine.

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          Author and article information

          Journal
          Eur J Neurosci
          The European journal of neuroscience
          Wiley
          0953-816X
          0953-816X
          Sep 2004
          : 20
          : 6
          Affiliations
          [1 ] Department of Pharmacology, University of Tennessee Health Science Center, 874 Union Avenue, Memphis, TN 38163, USA. jmwilliams@utmem.edu
          Article
          EJN3618
          10.1111/j.1460-9568.2004.03618.x
          15355331
          a37a96f2-ba1f-4b69-a0f3-a162311930df
          History

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