5-HT1A receptor sensitivity in 5-HT1B receptor KO mice is unaffected by chronic fluvoxamine treatment

The 5-HT1B receptor has been implicated in disorders such as depression, anxiety and obsessive–compulsive disorder. In mice lacking the 5-HT1B receptor (5-HT1B knockout mice), important changes in physiology and behavior exist. In the absence of presynaptic 5-HT1B receptor inhibition, chronic SSRI treatment may differentially affect 5-HT1A 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-HT1A receptor desensitization in 5-HT1B knockout mice. Moreover, as 5-HT1B 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-HT1B knockout mice were investigated.The stress-reducing effect of the 5-HT1A receptor agonist flesinoxan on increases in body temperature, heart rate and locomotor activity was similar in wild type and 5-HT1B knockout mice before and after chronic 21-day treatment with the SSRI fluvoxamine, indicating no apparent alteration of 5-HT1A receptor sensitivity in 5-HT1B knockout mice. Also, chronic SSRI treatment did not alter the increased stress reactivity to mild environmental stressors in 5-HT1B knockout mice.We demonstrate that no apparent differences in 5-HT1A receptor sensitivity occur between 5-HT1B knockout and wild type mice after chronic fluvoxamine treatment. Also, the hyperreactive phenotype of 5-HT1B knockout mice is unresponsive to chronic SSRI treatment. Taken together, these results indicate that constitutive absence of 5-HT1B receptors does not result in adaptive changes in 5-HT1A receptor functionality and that chronic SSRI treatment does not modify stress reactivity in 5-HT1B knockout mice.