Glutamate-dopamine crosstalk in the rat prefrontal cortex is modulated by Alpha7 nicotinic receptors and potentiated by PNU-120596.
The aim of this study was to explore the modulation by alpha7 nicotinic receptors (nAChRs) of dopamine and glutamate release in the rat prefrontal cortex where these receptors are implicated in attentional processes and are therapeutic targets for cognitive deficits. The presence of presynaptic alpha7 nAChRs on glutamate terminals is supported by the ability of the subtype-selective agonist Compound A to evoke [(3)H]D-aspartate release from synaptosomes: This response was potentiated by the selective allosteric potentiator PNU-120596 and blocked by alphabungarotoxin. Compound A also evoked dopamine overflow in the prefrontal cortex in vivo, and this was potentiated by PNU-120596. alpha7 nAChR-evoked [(3)H]dopamine release from tissue prisms in vitro was blocked by antagonists of NMDA and AMPA receptors. These data are consistent with a model in which alpha7 nAChRs present on glutamate terminals increase glutamate release that (1) contributes to presynaptic facilitation and synaptic plasticity and (2) co-ordinately enhances dopamine release from neighbouring boutons.
Livingstone
Phil D
PD
Department of Biology & Biochemistry, University of Bath, Bath, BA2 7AY, UK.
Dickinson
Jane A
JA
Srinivasan
Jayaraman
J
Kew
James N C
JN
Wonnacott
Susan
S
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology; D017551:Microdialysis; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013574:Synaptosomes; D064569:alpha7 Nicotinic Acetylcholine Receptor
C508388:1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)urea; C579165:Chrna7 protein, rat; D018691:Excitatory Amino Acid Antagonists; D007555:Isoxazoles; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D010671:Phenylurea Compounds; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005973:Glutamine; D001224:Aspartic Acid; D000109:Acetylcholine; D004298:Dopamine
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