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Second-by-second analysis of alpha 7 nicotine receptor regulation of glutamate release in the prefrontal cortex of awake rats.
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2009 (English)In: Synapse, ISSN 0887-4476, E-ISSN 1098-2396, Vol. 63, no 12Article in journal (Refereed) Published
Abstract [en]

These experiments utilized an enzyme-based microelectrode selective for the second-by-second detection of extracellular glutamate to reveal the alpha 7-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 microg/0.4 microl) or the selective alpha 7 agonist choline (2.0 mM/0.4 microl). The selectivity of drug-induced glutamate release was assessed in subgroups of animals pretreated with the alpha 7 antagonist, alpha-bungarotoxin (alpha-BGT, 10 microM), or kynurenine (10 microM) the precursor of the astrocyte-derived, negative allosteric alpha 7 modulator kynurenic acid. Local administration of nicotine increased glutamate signals (maximum amplitude = 4.3 +/- 0.6 microM) that were cleared to baseline levels in 493 +/- 80 seconds. Pretreatment with alpha-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 microM). In contrast to nicotine-evoked glutamate release, choline-evoked signals were cleared more quickly (28 +/- 6 seconds) and pretreatment with alpha-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 alpha 7- and non-alpha 7-mediated. Furthermore, these data may also provide a mechanism underlying the recent focus on alpha 7 full and partial agonists as therapeutic agents in the treatment of cortically mediated cognitive deficits in schizophrenia.

Place, publisher, year, edition, pages
2009. Vol. 63, no 12
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-283235DOI: 10.1002/syn.20693PubMedID: 19637277OAI: oai:DiVA.org:uu-283235DiVA: diva2:918841
Available from: 2016-04-12 Created: 2016-04-12 Last updated: 2016-04-12

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