Combined treatment with citalopram and buspirone: effects on serotonin 5-HT2A and 5-HT2C receptors in the rat brain.
BACKGROUND
We wanted to elucidate whether the proposed advantages of citalopram-buspirone combination treatment are related to changes in 5-HT(2A/C) receptor-mediated neurotransmission.


METHODS
The affinity of buspirone to 5-HT2A and 5-HT2C receptors was measured in vitro, and the influence of buspirone on 5-HT2C receptor-mediated phosphoinositide hydrolysis was estimated. Four groups of rats received citalopram (10 mg/kg), buspirone (6 mg/kg), citalopram-buspirone combination, or saline once a day s.c. for 14 days. Treatment effects on 5-HT2A and 5-HT2C receptors were investigated by receptor autoradiography with antagonist and agonist radioligands.


RESULTS
Buspirone was found to be a weak 5-HT2C receptor antagonist, with a low affinity for 5-HT2A and 5-HT2C receptors. Repeated buspirone-citalopram combination treatment markedly decreased [3H]ketanserin and [125I]DOI binding to 5-HT2A receptors. Repeated administration of buspirone and buspirone-citalopram combination increased the affinity of [3H]mesulergine toward 5-HT2C receptors, and buspirone-citalopram combination also decreased [125I]DOI binding to 5-HT2C receptors.


CONCLUSIONS
We suggest that downregulation of brain 5-HT2A receptors and possibly of 5-HT2C receptor agonist sites is involved in the beneficial clinical effects of buspirone-SSRI augmentation treatment. Furthermore, a conversion of brain 5-HT2C receptors from high- to low-affinity state may provide an additional mechanism for the anti-anxiety effects of buspirone.
Syvälahti
E
E
Department of Pharmacology and Clinical Pharmacology, University of Turku, 20520 Turku, Finland. erkka.syvalahti@utu.fi
Penttilä
J
J
Majasuo
H
H
Pälvimäki
E-P
EP
Laakso
A
A
Hietala
J
J
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects*; D002065:Buspirone / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D006868:Hydrolysis; D007091:Image Processing, Computer-Assisted; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology
D000662:Amphetamines; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D004873:Ergolines; D010716:Phosphatidylinositols; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D015283:Citalopram; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C031649:mesulergine; D002065:Buspirone