N-methyl-D-aspartate receptor antagonists counteract the long lasting 5-HT1A receptor-induced attenuation of postsynaptic responses in the rat in vivo.
The effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists dizocilpine and phenycyclidine, the competitive NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the antagonist at the glycine modulatory site of the NMDA receptor, 3-amino-1-hydroxy-2-pyrrolidone (HA-966) on the long lasting attenuation of some post-synaptic 5-HT1A receptor-mediated responses in rats (increased corticosterone secretion and inhibition of the cage leaving response) produced by a single injection of the 5-hydroxytryptamine1A (5-HT1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was studied. It was found that these antagonists counteracted the attenuation of these responses at dose levels known to block the NMDA receptor-ion channel complex in vivo. It is concluded that the long lasting attenuation of postsynaptic responses after a 5-HT1A receptor agonist is initiated through stimulation of glutamate NMDA receptors indicating a functional interaction between the 5-HT and glutamate systems in at least two different models.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D016291:Dizocilpine Maleate / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012768:Shivering / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D007473:Ion Channels; D010879:Piperazines; D011760:Pyrrolidinones; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D016291:Dizocilpine Maleate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C001369:1-hydroxy-3-amino-2-pyrrolidone; D010622:Phencyclidine; D003345:Corticosterone