Single doses of MK-801, a non-competitive antagonist of NMDA receptors, increase the number of 5-HT1A serotonin receptors in the rat brain.
In the present study, we investigated the impact of MK-801, a non-competitive NMDA receptor antagonist, on the density of serotonergic receptors of the 5-HT1A subtype and on the metabolism of serotonin in various regions of the rat brain containing terminals and cell bodies of serotonergic neurons. The binding of [3H]8-OH-DPAT to 5-HT1A serotonin receptors was increased after MK-801 (0.4 mg/kg) as was shown by autoradiographic studies in the frontal, cingulate and part of enthorinal cortex, subregions of the hippocampus and raphe nuclei. The above receptor changes were observed at 2 h and, in some brain regions, at 24 h after MK-801. In saturation binding studies, an increase in the Bmax value in the rat hippocampus was found after MK-801 (0.4 mg/kg) while no changes being noted in the Kd value. MK-801 (0.4 mg/kg) increased the concentration of the serotonin metabolite 5-HIAA in the prefrontal cortex and hippocampus, respectively, at 2 and 3 or 3 h after administration, being without effect on the level of serotonin. In the dorsal raphe nucleus, MK-801 (0.4 mg/kg) decreased the level of serotonin without affecting the level 5-HIAA (0.5 h after administration) or increased the level of 5-HIAA without altering the concentration of serotonin (3 h after administration). It is concluded that single administration of MK-801 may alter the density of serotonergic 5-HT1A receptors and in consequence influence the function of the central nervous system associated with activation of 5-HT1A receptors.
Wedzony
K
K
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.nfwedzon@cyf-kr.edu.pl
Maćkowiak
M
M
Czyrak
A
A
Fijał
K
K
Michalska
B
B
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D016291:Dizocilpine Maleate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin