Authors: Meredith A Fox Micaella G Panessiti F Scott Hall George R Uhl Dennis L Murphy
Publish Date: 2013/02/17
Volume: 227, Issue: 4, Pages: 685-695
Abstract
In the open field mean turn angle and meandering were decreased in DAT knockout DATKO mice DATKO mice displayed increased hyperactivity increased velocity less time immobile and a failure to habituate over time in the open field unlike their DAT wildtype DATWT and heterozygous DATHET littermates DATKO mice buried fewer marbles than DATWT and HET mice in an assessment of compulsivelike behaviors likely due to extreme hyperactivity and related inattention Stereotypical head weaving was increased in untreated DATKO mice Following administration of the 5HT1A/7 agonist 8hydroxy2dinpropylaminotetralin 8OHDPAT stereotypical head weaving and forepaw treading were increased more in DATKO mice than in DATWT or HET mice By contrast head twitches induced by treatment with the 5HT2A/2C agonist ±25dimethoxy4iodophenyl2aminopropane DOI were similar in mice of all three DAT genotypes 5HT1A autoreceptor function was intact in DATKO mice Compared to DATWT mice serotonin levels were increased in DATHET and KO mice in frontal cortex and hippocampus respectively and serotonin turnover rates were increased ∼30 in the striatum of DATKO miceThese findings extend and confirm prior behavioral and biochemical characterization of DATKO mice Hyperactivity stereotypy and perseverative behaviors are increased in these mice with brainarea specific increases in serotonin levels and serotonin turnover and marked increases in postsynaptic 5HT1A receptormediated stereotypic responsesThis research was supported by the National Institute of Mental Health NIMH and the National Institute on Drug Abuse NIDA Intramural Research Programs The authors thank Teresa Tolliver for her generous technical assistance with the HPLC experiments and for her continued assistance with animal care and Dr Pablo Moya for his helpful scientific comments and suggestions
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