The effect of chronic selective serotonin reuptake inhibitor treatment on serotonin 1B receptor sensitivity and HPA axis activity.
The authors have investigated 5-HT 1B receptor function in prefrontal cortex and dorsal hippocampus as well as the HPA axis response after subchronic (24 h) and chronic (15 days) treatment with the SSRI citalopram. All experiments were carried out in presence of citalopram to prevent rapid resensitization of the 5-HT(1B) receptors. Moreover, this more closely resembles the clinical situation. The concentration of citalopram was measured in both brain areas to ensure comparable levels in the different treatment groups. Using microdialysis, the authors found that under those conditions the effect of the 5-HT 1B receptor antagonists SB 224289 and the mixed 5-HT 1B/1D receptor antagonist GR 127935 on extracellular levels of 5-HT was unaltered by duration of treatment. Basal levels of 5-HT, however, were increased in the dorsal hippocampus following chronic treatment. In addition, plasma levels of the catecholamines adrenaline and noradrenaline and the HPA axis hormones ACTH and corticosterone were all decreased after chronic treatment.
Jongsma
Minke E
ME
Department of Psychiatry, University Medical Centre Groningen, Groningen, The Netherlands. M.E.Jongsma@psy.umcg.nl
Bosker
Fokko J
FJ
Cremers
Thomas I F H
TI
Westerink
Ben H C
BH
den Boer
Johan A
JA
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001921:Brain / Q000378:metabolism; D002395:Catecholamines / Q000097:blood; D015283:Citalopram / Q000493:pharmacokinetics / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D005110:Extracellular Space / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D017551:Microdialysis; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010881:Piperidones / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects*; D017661:Receptors, Presynaptic / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology
D000324:Adrenocorticotropic Hormone; D002395:Catecholamines; D015283:Citalopram; D003345:Corticosterone; D010069:Oxadiazoles; D010879:Piperazines; D010881:Piperidones; D044302:Receptor, Serotonin, 5-HT1B; D017661:Receptors, Presynaptic; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D013141:Spiro Compounds; C108518:SB 22489G; C090701:GR 127935