Second-by-second analysis of alpha 7 nicotine receptor regulation of glutamate release in the prefrontal cortex of awake rats

Asa Konradsson-Geuken, Clelland R. Gash, Kathleen Alexander, Francois Pomerleau, Peter Huettl, Greg A. Gerhardt, John P. Bruno

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


These experiments utilized an enzyme-based microelectrode selective for the second-by-second detection of extracellular glutamate to reveal the α7-based nicotinic modulation of glutamate release in the prefrontal cortex (PFC) of freely moving rats. Rats received intracortical infusions of the nonselective nicotinic agonist nicotine (12.0 mM, 1.0 μg/0.4 μl) or the selective α7 agonist choline (2.0 mM/0.4 μl). The selectivity of drug-induced glutamate release was assessed in subgroups of animals pretreated with the α7 antagonist, α-bungarotoxin (α-BGT, 10 μM), or kynurenine (10 μM) the precursor of the astrocyte-derived, negative allosteric α7 modulator kynurenic acid. Local administration of nicotine increased glutamate signals (maximum amplitude = 4.3 ± 0.6 μM) that were cleared to baseline levels in 493 ± 80 seconds. Pretreatment with α-BGT or kynurenine attenuated nicotine-induced glutamate by 61% and 60%, respectively. Local administration of choline also increased glutamate signals (maximum amplitude = 6.3 ± 0.9 μM). In contrast to nicotine-evoked glutamate release, choline-evoked signals were cleared more quickly (28 ± 6 seconds) and pretreatment with α-BGT or kynurenine completely blocked the stimulated glutamate release. Using a method that reveals the temporal dynamics of in vivo glutamate release and clearance, these data indicate a nicotinic modulation of cortical glutamate release that is both α7- and non-α7-mediated. Furthermore, these data may also provide a mechanism underlying the recent focus on α7 full and partial agonists as therapeutic agents in the treatment of cortically mediated cognitive deficits in schizophrenia.

Original languageEnglish
Pages (from-to)1069-1082
Number of pages14
Issue number12
StatePublished - Dec 2009


  • Alpha 7
  • Amperometry
  • Biosensor
  • Glutamate
  • Nicotine
  • Prefrontal cortex

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Second-by-second analysis of alpha 7 nicotine receptor regulation of glutamate release in the prefrontal cortex of awake rats'. Together they form a unique fingerprint.

Cite this