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Pharmacopsychiatry 2006; 39(1): 1-8
DOI: 10.1055/s-2006-931470
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Combined Treatment with Citalopram and Buspirone: Effects on Serotonin 5-HT2A and 5-HT2C Receptors in the Rat Brain

E. Syvälahti1 , J. Penttilä2 , 3 , H. Majasuo4 , E.-P. Pälvimäki5 , A. Laakso1 , 5 , J. Hietala2 , 6
  • 1Department of Pharmacology and Clinical Pharmacology, University of Turku, 20520 Turku, Finland
  • 2Department of Psychiatry, Turku University Central Hospital, 20520 Turku, Finland
  • 3Department of Psychiatry, Päijät-Häme Central Hospital, 15850 Lahti, Finland
  • 4Department of Anesthesiology and Intensive care, Turku University Central Hospital, 20520 Turku, Finland
  • 5Department of Neurosurgery, Helsinki University Central Hospital, 00029, Helsinki, Finland
  • 6Turku PET Centre, Turku University Central Hospital, 20520 Turku, Finland
Further Information

Publication History

Received: 14.3.2005 Revised: 19.7.2005

Accepted: 30.8.2005

Publication Date:
02 February 2006 (online)

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Introduction: We wanted to elucidate whether the proposed advantages of citalopram-buspirone combination treatment are related to changes in 5-HT2A/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. Discussion: 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.

Abbreviations

Bmax:maximum receptor density

DOI:(+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane

5-HT:serotonin (5-hydroxytryptamine)

IP:inositol monophosphate

K d:equilibrium dissociation constant (affinity)

K i:inhibition constant

KRB:Krebs-bicarbonate

PI:phosphoinositide

1-PP:1-(2-pyrimidinyl)piperazine

SSRI:selective serotonin reuptake inhibitor

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Prof. Erkka Syvälahti

Department of Pharmacology and Clinical Pharmacology

University of Turku

Itäinen Pitkäkatu 4 B

20520 Turku

FINLAND

Phone: +358 2 333 7582

Fax: +358 2 333 7216

Email: erkka.syvalahti@utu.fi