TY - JOUR
T1 - 5-HT(1A) receptor sensitivity in 5-HT(1B) receptor KO mice is unaffected by chronic fluvoxamine treatment
AU - Vinkers, C.H.
AU - Groenink, L.
AU - Pattij, T.
AU - Olivier, B.
AU - Bouwknecht, J.A.
N1 - Copyright © 2011 Elsevier B.V. All rights reserved.
PY - 2011/9/30
Y1 - 2011/9/30
N2 - The 5-HT(1B) receptor has been implicated in disorders such as depression, anxiety and obsessive-compulsive disorder. In mice lacking the 5-HT(1B) receptor (5-HT(1B) knockout mice), important changes in physiology and behavior exist. In the absence of presynaptic 5-HT(1B) receptor inhibition, chronic SSRI treatment may differentially affect 5-HT(1A) receptor functionality. The present studies tested the hypothesis that chronically reducing 5-HT transporter (5-HTT) function with selective serotonin reuptake inhibitor (SSRI) treatment would accelerate 5-HT(1A) receptor desensitization in 5-HT(1B) knockout mice. Moreover, as 5-HT(1B) knockout mice have been found to display exaggerated autonomic and locomotor responses to environmental stressors, the effects of chronic SSRI treatment on the hyperreactive phenotype of 5-HT(1B) knockout mice were investigated. The stress-reducing effect of the 5-HT(1A) receptor agonist flesinoxan on increases in body temperature, heart rate and locomotor activity was similar in wild type and 5-HT(1B) knockout mice before and after chronic 21-day treatment with the SSRI fluvoxamine, indicating no apparent alteration of 5-HT(1A) receptor sensitivity in 5-HT(1B) knockout mice. Also, chronic SSRI treatment did not alter the increased stress reactivity to mild environmental stressors in 5-HT(1B) knockout mice. We demonstrate that no apparent differences in 5-HT(1A) receptor sensitivity occur between 5-HT(1B) knockout and wild type mice after chronic fluvoxamine treatment. Also, the hyperreactive phenotype of 5-HT(1B) knockout mice is unresponsive to chronic SSRI treatment. Taken together, these results indicate that constitutive absence of 5-HT(1B) receptors does not result in adaptive changes in 5-HT(1A) receptor functionality and that chronic SSRI treatment does not modify stress reactivity in 5-HT(1B) knockout mice.
AB - The 5-HT(1B) receptor has been implicated in disorders such as depression, anxiety and obsessive-compulsive disorder. In mice lacking the 5-HT(1B) receptor (5-HT(1B) knockout mice), important changes in physiology and behavior exist. In the absence of presynaptic 5-HT(1B) receptor inhibition, chronic SSRI treatment may differentially affect 5-HT(1A) receptor functionality. The present studies tested the hypothesis that chronically reducing 5-HT transporter (5-HTT) function with selective serotonin reuptake inhibitor (SSRI) treatment would accelerate 5-HT(1A) receptor desensitization in 5-HT(1B) knockout mice. Moreover, as 5-HT(1B) knockout mice have been found to display exaggerated autonomic and locomotor responses to environmental stressors, the effects of chronic SSRI treatment on the hyperreactive phenotype of 5-HT(1B) knockout mice were investigated. The stress-reducing effect of the 5-HT(1A) receptor agonist flesinoxan on increases in body temperature, heart rate and locomotor activity was similar in wild type and 5-HT(1B) knockout mice before and after chronic 21-day treatment with the SSRI fluvoxamine, indicating no apparent alteration of 5-HT(1A) receptor sensitivity in 5-HT(1B) knockout mice. Also, chronic SSRI treatment did not alter the increased stress reactivity to mild environmental stressors in 5-HT(1B) knockout mice. We demonstrate that no apparent differences in 5-HT(1A) receptor sensitivity occur between 5-HT(1B) knockout and wild type mice after chronic fluvoxamine treatment. Also, the hyperreactive phenotype of 5-HT(1B) knockout mice is unresponsive to chronic SSRI treatment. Taken together, these results indicate that constitutive absence of 5-HT(1B) receptors does not result in adaptive changes in 5-HT(1A) receptor functionality and that chronic SSRI treatment does not modify stress reactivity in 5-HT(1B) knockout mice.
KW - Animals
KW - Body Temperature/drug effects
KW - Fluvoxamine/pharmacology
KW - Gene Knockout Techniques
KW - Heart Rate/drug effects
KW - Male
KW - Mice
KW - Motor Activity/drug effects
KW - Receptor, Serotonin, 5-HT1A/metabolism
KW - Receptor, Serotonin, 5-HT1B/deficiency
KW - Serotonin Uptake Inhibitors/pharmacology
KW - Stress, Physiological/drug effects
KW - Time Factors
U2 - 10.1016/j.ejphar.2011.06.018
DO - 10.1016/j.ejphar.2011.06.018
M3 - Article
C2 - 21723276
VL - 667
SP - 250
EP - 257
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -