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Lookup NU author(s): Dr Mohammed Shoaib
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Nicotine enhances attentional and working memory aspects of executive function in the prefrontal cortex (PFC) where dopamine plays a major role. Here, we have determined the nicotinic acetylcholine receptor (nAChR) subtypes that can modulate dopamine release in rat PFC using subtype-selective drugs. Nicotine and 5-Iodo-A-85380 (beta 2* selective) elicited [H-3]dopamine release from both PFC and striatal prisms in vitro and dopamine overflow from medial PFC in vivo. Blockade by dihydro-beta-erythroidine supports the participation of beta 2* nAChRs. However, insensitivity of nicotine-evoked [H-3]dopamine release to alpha-conotoxin-MII in PFC prisms suggests no involvement of alpha 6 beta 2* nAChRs, in contrast to the striatum, and this distinction is supported by immunoprecipitation of nAChR subunits from these tissues. The alpha 7 nAChR-selective agonists choline and Compound A also promoted dopamine release from PFC in vitro and in vivo, and their effects were enhanced by the alpha 7 nAChR-selective allosteric potentiator PNU-120596 and blocked by specific antagonists. DNQX and MK801 inhibited [H-3]dopamine release evoked by choline and PNU-120596, suggesting crosstalk between alpha 7 nAChRs, glutamate and dopamine in the PFC. In vivo, systemic (but not local) administration of PNU-120596, in the absence of agonist, facilitated dopamine overflow in the medial PFC, consistent with the activation of extracortical alpha 7 nAChRs by endogenous acetylcholine or choline. These data establish that both beta 2* and alpha 7 nAChRs can modulate dopamine release in the PFC in vitro and in vivo. Through their distinct actions on dopamine release, these nAChR subtypes could contribute to executive function, making them specific therapeutic targets for conditions such as schizophrenia and attention deficit hyperactivity disorder.
Author(s): Livingstone PD, Srinivasan J, Kew JN, Dawson LA, Gotti C, Moretti M, Shoaib M, Wonnacott S
Publication type: Article
Publication status: Published
Journal: European Journal of Neuroscience
ISSN (print): 0953-816X
ISSN (electronic): 1460-9568
Publisher: Wiley-Blackwell Publishing Ltd.
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