In vivo regulation of serotonin 5-HT2A receptors in rat brain by subchronic administration of sigma receptor ligand NE-100.
In the present study, we examined the effect of the novel sigma receptor ligand NE-100 on 5-hydroxytryptamine-2A (5-HT2A) receptor binding in rat brain using an in vivo approach. Rats received intraperitoneal injections of either vehicle (1 ml/kg) or NE-100 (3 mg/kg) twice daily for 14 days. The in vivo binding of [3H]RP 62203, a selective 5-HT2A receptor radioligand, to 5-HT2A receptors in the rat brain was examined at 1, 3 or 7 days after final treatment. The specific binding of [3H]RP 62203 in the frontal cortex, parietal cortex and occipital cortex 1 day after subchronic administration of NE-100 was significantly increased as compared to animals treated with vehicle. In contrast, specific binding in the frontal cortex and parietal cortex 3 days after subchronic administration of NE-100 was significantly decreased as compared with the vehicle treated group. Seven days after the last injection of NE-100 or vehicle, there were no significant differences between the NE-100 and vehicle treated groups in [3H]RP 62203 binding in all the regions examined except for the hippocampus. These findings indicate that subchronic treatment with NE-100 may regulate the in vivo binding characteristics of 5-HT2A receptors in the cerebral cortex of rat brain.
Hashimoto
K
K
Division of Cortical Function Disorders, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan. hashiken@mxj.meshnet.or.jp
Narita
N
N
Tomitaka
S
S
Iyo
M
M
Minabe
Y
Y
D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003499:Cyclic S-Oxides / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008297:Male; D009281:Naphthalenes / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism
D000840:Anisoles; D014150:Antipsychotic Agents; D003499:Cyclic S-Oxides; D008024:Ligands; D009281:Naphthalenes; D011437:Propylamines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D017480:Receptors, sigma; D012702:Serotonin Antagonists; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; C070475:fananserin