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The 5‐HT 1A receptor agonist 8‐OH‐DPAT prevents prefrontocortical glutamate and serotonin release in response to blockade of cortical NMDA receptors
Author(s) -
Calcagno E.,
Carli M.,
Invernizzi R. W.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03600.x
Subject(s) - microdialysis , agonist , 5 ht receptor , extracellular , nmda receptor , chemistry , glutamate receptor , serotonin , receptor , receptor antagonist , 8 oh dpat , medicine , endocrinology , 5 ht1a receptor , stimulation , pharmacology , antagonist , biology , biochemistry
We studied the role of 5‐HT 1A receptors in controlling the release of glutamate (GLU) in the medial prefrontal cortex (mPFC) of conscious rats with the in vivo microdialysis technique. The effect of the 5‐HT 1A receptor agonist 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin infused in the prefrontal cortex was examined under basal conditions and on the rise of extracellular GLU (+106%) induced by co‐infusion of the competitive N ‐methyl‐ d ‐aspartate receptor antagonist 3‐[(R)‐2‐carboxypiperazin‐4yl]‐propyl‐1‐phosphonic acid (CPP). 8‐OH‐DPAT (0.3 and 3 μ m ) had no effect on basal extracellular GLU, but the higher concentration completely abolished the rise of extracellular GLU induced by CPP. CPP also increased extracellular serotonin (5‐HT) in the mPFC (+50%) and this effect was antagonized by 3 μ m 8‐OH‐DPAT which, by itself, had no effect on basal 5‐HT release. The effects of 8‐OH‐DPAT on extracellular GLU and 5‐HT were reversed by the 5‐HT 1A receptor antagonist WAY100 635 (100 μ m ), indicating a selective involvement of 5‐HT 1A receptors. WAY100 635 had no effect by itself. These results show that the stimulation of cortical 5‐HT 1A receptors prevents the CPP‐evoked rise of extracellular GLU and 5‐HT and suggest that these effects may contribute to the ability of intracortical 8‐OH‐DPAT to counteract cognitive deficits caused by the blockade of NMDA receptors.