Abstract
The anatomical distribution and pharmacology of serotonin 6 receptors (5-HT6Rs) implicate them as contributors to the serotonergic regulation of complex behavior. To complement the limited range of pharmacological tools available to examine 5-HT6R function, we have generated a mouse line bearing a constitutive null mutation of the 5-HT6R gene. No perturbations of baseline behavior were noted in a wide array of assays pertinent to multiple neurobehavioral processes. However, 5-HT6R mutant mice demonstrated reduced responses to the ataxic and sedative effects of ethanol. No differences in ethanol metabolism were evident between wild-type and 5-HT6R mutant mice. These findings implicate 5-HT6Rs in the serotonergic modulation of responses to ethanol.
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Acknowledgements
This research was funded in part by grants from the American Federation for Aging Research (SJB), Department of Veteran's Affairs (HMC), National Alliance for Research on Schizophrenia and Depression (HMC), and Program for Minority Research Training in Psychiatry 5T32MH19126 (HMC). We thank Drs Mark Hamblin and Ruth Kohen for a 5-HT6 receptor genomic fragment, Dr Roger Pederson for 129-derived embryonic stem cells, and Dr Warren Hirst for use of 125I-SB258585. We also thank Jean Danao, Irene Yun, Aileen Sweeney, and Jed Holtzman for their technical skills and support.
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Bonasera, S., Chu, HM., Brennan, T. et al. A Null Mutation of the Serotonin 6 Receptor Alters Acute Responses to Ethanol. Neuropsychopharmacol 31, 1801–1813 (2006). https://doi.org/10.1038/sj.npp.1301030
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DOI: https://doi.org/10.1038/sj.npp.1301030
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