The 5-HT(1A) receptor agonist 8-OH-DPAT prevents prefrontocortical glutamate and serotonin release in response to blockade of cortical NMDA receptors.
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 microm) 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 microm 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 microm), 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.
Calcagno
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Istituto di Richerche Farmacologiche Mario Negri, Department of Neuroscience, Milan, Italy.
Carli
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Invernizzi
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003956:Dialysis / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004563:Electrochemistry / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D011725:Pyridines; D016194:Receptors, N-Methyl-D-Aspartate; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D018698:Glutamic Acid; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid