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{"title"=>"Serotonin/dopamine interactions in a hyperactive mouse: Reduced serotonin receptor 1B activity reverses effects of dopamine transporter knockout", "type"=>"journal", "authors"=>[{"first_name"=>"Frank Scott", "last_name"=>"Hall", "scopus_author_id"=>"37025945700"}, {"first_name"=>"Ichiro", "last_name"=>"Sora", "scopus_author_id"=>"35406969700"}, {"first_name"=>"René", "last_name"=>"Hen", "scopus_author_id"=>"7005852886"}, {"first_name"=>"George R.", "last_name"=>"Uhl", "scopus_author_id"=>"7102216410"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"600783688", "scopus"=>"2-s2.0-84918578872", "pmid"=>"25514162", "sgr"=>"84918578872", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0115009"}, "id"=>"891fd7ac-a57c-3fca-8b68-e2a92f988f63", "abstract"=>"Knockout (KO) mice that lack the dopamine transporter (SL6A3; DAT) display increased locomotion that can be attenuated, under some circumstances, by administration of drugs that normally produce psychostimulant-like effects, such as amphetamine and methylphenidate. These results have led to suggestions that DAT KO mice may model features of attention deficit hyperactivity disorder (ADHD) and that these drugs may act upon serotonin (5-HT) systems to produce these unusual locomotor decreasing effects. Evidence from patterns of brain expression and initial pharmacologic studies led us to use genetic and pharmacologic approaches to examine the influence of altered 5-HT1B receptor activity on hyperactivity in DAT KO mice. Heterozygous 5-HT1B KO and pharmacologic 5-HT1B antagonism both attenuated locomotor hyperactivity in DAT KO mice. Furthermore, DAT KO mice with reduced, but not eliminated, 5-HT1B receptor expression regained cocaine-stimulated locomotion, which was absent in DAT KO mice with normal levels of 5-HT1B receptor expression. Further experiments demonstrated that the degree of habituation to the testing apparatus determined whether cocaine had no effect on locomotion in DAT KO or reduced locomotion, helping to resolve differences among prior reports. These findings of complementation of the locomotor effects of DAT KO by reducing 5-HT1B receptor activity underscore roles for interactions between specific 5-HT receptors and dopamine (DA) systems in basal and cocaine-stimulated locomotion and support evaluation of 5-HT1B antagonists as potential, non-stimulant ADHD therapeutics.", "link"=>"http://www.mendeley.com/research/serotonindopamine-interactions-hyperactive-mouse-reduced-serotonin-receptor-1b-activity-reverses-eff", "reader_count"=>26, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>9, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>3, "Student > Master"=>6, "Other"=>2, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>9, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>3, "Student > Master"=>6, "Other"=>2, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>5, "Neuroscience"=>7, "Arts and Humanities"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Neuroscience"=>{"Neuroscience"=>7}, "Psychology"=>{"Psychology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Germany"=>1}, "group_count"=>2}

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• http://doi.org/10.1007/s11596-018-1912-3
• http://doi.org/10.1016/j.biopsych.2020.01.007
• http://doi.org/10.1016/j.ajpath.2016.10.011
• http://doi.org/10.1007/s11064-021-03275-4
• http://doi.org/10.3109/01677063.2016.1144751
• http://doi.org/10.1021/acschemneuro.5b00029
• http://doi.org/10.1016/j.neubiorev.2016.10.029
• http://doi.org/10.1016/j.ntt.2019.106834
• http://doi.org/10.3389/fpsyt.2017.00046
• http://doi.org/10.1186/s13229-018-0243-3

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/1844987"], "description"=>"<p>Cocaine-induced locomotor activity in DAT/5-HT1B KO mice is expressed as absolute difference s from baseline, preinjection values. Post hoc analysis by 1 way ANOVA for COCAINE concentration revealed significant effects of cocaine for all genotypes except DAT −/−5-HT1B +/+ and DAT −/−5-HT1B −/−. Data are represented as mean ± SEM.</p>", "links"=>[], "tags"=>["ht", "Reduced Serotonin Receptor 1 B Activity Reverses Effects", "locomotion", "1b", "receptor", "adhd", "attenuated locomotor hyperactivity", "DAT KO", "attention deficit hyperactivity disorder", "Dopamine Transporter Knockout Knockout", "SL 6A DAT", "DAT KO mice"], "article_id"=>1272529, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Frank Scott Hall", "Ichiro Sora", "Rene Hen", "George R. Uhl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115009.g003", "stats"=>{"downloads"=>0, "page_views"=>37, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Experiment_1_Cocaine_induced_locomotion_in_well_habituated_DAT_5_HT1B_KO_mice_/1272529", "title"=>"Experiment 1: Cocaine-induced locomotion in well habituated DAT/5-HT1B KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-16 02:54:00"}
• {"files"=>["https://ndownloader.figshare.com/files/1844988"], "description"=>"<p>(A) Time-course of locomotor activity during the first habituation session in DAT/5-HT1B KO mice (9 genotypes: DAT +/+5-HT1B +/+, DAT −/−5-HT1B +/+, DAT +/+5-HT1B −/−, DAT +/−5-HT1B −/−, DAT −/−5-HT1B +/−, DAT −/−5-HT1B −/−) expressed in terms of total distance traveled. (B) Cocaine-induced locomotor activity in DAT/5-HT1B KO mice expressed as absolute difference from saline (total activity after cocaine injection – total activity after saline injection). Data are represented as mean ± SEM.</p>", "links"=>[], "tags"=>["ht", "Reduced Serotonin Receptor 1 B Activity Reverses Effects", "locomotion", "1b", "receptor", "adhd", "attenuated locomotor hyperactivity", "DAT KO", "attention deficit hyperactivity disorder", "Dopamine Transporter Knockout Knockout", "SL 6A DAT", "DAT KO mice"], "article_id"=>1272531, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Frank Scott Hall", "Ichiro Sora", "Rene Hen", "George R. Uhl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115009.g004", "stats"=>{"downloads"=>1, "page_views"=>43, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Experiment_2_Locomotor_activity_in_combined_DAT_5_HT1B_KO_mice_short_habituation_sessions_/1272531", "title"=>"Experiment 2: Locomotor activity in combined DAT/5-HT1B KO mice: short habituation sessions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-16 02:54:00"}
• {"files"=>["https://ndownloader.figshare.com/files/1844991"], "description"=>"<p>Time-course of saline and cocaine-induced locomotor activity in DAT/5-HT1B KO mice, represented separately for each genotype. Cocaine increased locomotion in all DAT +/+ and DAT +/− genotypes (p<0.01), and reduced locomotion in all DAT −/− genotypes (p<0.01) except DAT −/−5-HT1B, which was confirmed by individual ANOVA comparing saline and cocaine locomotion for each genotype. Data are represented as mean ± SEM.</p>", "links"=>[], "tags"=>["ht", "Reduced Serotonin Receptor 1 B Activity Reverses Effects", "locomotion", "1b", "receptor", "adhd", "attenuated locomotor hyperactivity", "DAT KO", "attention deficit hyperactivity disorder", "Dopamine Transporter Knockout Knockout", "SL 6A DAT", "DAT KO mice"], "article_id"=>1272533, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Frank Scott Hall", "Ichiro Sora", "Rene Hen", "George R. Uhl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115009.g005", "stats"=>{"downloads"=>4, "page_views"=>128, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Experiment_2_Time_course_of_locomotor_activity_in_DAT_5_HT1B_KO_mice_short_habituation_sessions_/1272533", "title"=>"Experiment 2: Time-course of locomotor activity in DAT/5-HT1B KO mice, short habituation sessions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-16 02:54:00"}
• {"files"=>["https://ndownloader.figshare.com/files/1844993"], "description"=>"<p>Time-course locomotor activity in DAT −/− and DAT +/+ mice after injection with 0, 5, 10, or 20 mg/kg SB 224289. Data are represented as mean ± the SEM.</p>", "links"=>[], "tags"=>["ht", "Reduced Serotonin Receptor 1 B Activity Reverses Effects", "locomotion", "1b", "receptor", "adhd", "attenuated locomotor hyperactivity", "DAT KO", "attention deficit hyperactivity disorder", "Dopamine Transporter Knockout Knockout", "SL 6A DAT", "DAT KO mice"], "article_id"=>1272535, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Frank Scott Hall", "Ichiro Sora", "Rene Hen", "George R. Uhl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115009.g006", "stats"=>{"downloads"=>1, "page_views"=>69, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Experiment_3_The_effects_of_the_5_HT_antagonist_SB_224289_on_locomotor_activity_in_DAT_KO_and_WT_mice_/1272535", "title"=>"Experiment 3: The effects of the 5-HT antagonist SB 224289 on locomotor activity in DAT KO and WT mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-16 02:54:00"}
• {"files"=>["https://ndownloader.figshare.com/files/1844984"], "description"=>"<p>Time-course of locomotor activity during the first habituation session in DAT/5-HT1B KO mice (9 genotypes: DAT +/+5-HT1B +/+, DAT −/−5-HT1B +/+, DAT +/+5-HT1B −/−, DAT +/−5-HT1B −/−, DAT −/−5-HT1B +/−, DAT −/−5-HT1B −/−) expressed in terms of total distance traveled. Data are represented as mean ± SEM.</p>", "links"=>[], "tags"=>["ht", "Reduced Serotonin Receptor 1 B Activity Reverses Effects", "locomotion", "1b", "receptor", "adhd", "attenuated locomotor hyperactivity", "DAT KO", "attention deficit hyperactivity disorder", "Dopamine Transporter Knockout Knockout", "SL 6A DAT", "DAT KO mice"], "article_id"=>1272526, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Frank Scott Hall", "Ichiro Sora", "Rene Hen", "George R. Uhl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115009.g001", "stats"=>{"downloads"=>2, "page_views"=>88, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Experiment_1_Time_course_of_baseline_locomotor_activity_in_combined_DAT_5_HT1B_KO_mice_long_habituation_session_/1272526", "title"=>"Experiment 1: Time-course of baseline locomotor activity in combined DAT/5-HT1B KO mice: long habituation session.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-16 02:54:00"}
• {"files"=>["https://ndownloader.figshare.com/files/1844985"], "description"=>"<p>Total locomotor activity in DAT/5-HT1B KO mice (9 genotypes: DAT +/+5-HT1B +/+, DAT −/−5-HT1B +/+, DAT +/+5-HT1B −/−, DAT +/−5-HT1B −/−, DAT −/−5-HT1B +/−, DAT −/−5-HT1B −/−) expressed in terms of summed distance traveled during all of the 4 habituation sessions prior to drug (5, 10 and 20 mg/kg IP cocaine; C5, C10 and C20 respectively) or saline (SAL) injections. *Significant difference from DAT +/+5-HT1B +/+ mice based on Scheffe’s post hoc comparison (p<0.05). Data are represented as mean ± SEM.</p>", "links"=>[], "tags"=>["ht", "Reduced Serotonin Receptor 1 B Activity Reverses Effects", "locomotion", "1b", "receptor", "adhd", "attenuated locomotor hyperactivity", "DAT KO", "attention deficit hyperactivity disorder", "Dopamine Transporter Knockout Knockout", "SL 6A DAT", "DAT KO mice"], "article_id"=>1272527, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Frank Scott Hall", "Ichiro Sora", "Rene Hen", "George R. Uhl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115009.g002", "stats"=>{"downloads"=>0, "page_views"=>45, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Experiment_1_Baseline_locomotor_activity_in_well_habituated_combined_DAT_5_HT1B_KO_mice_/1272527", "title"=>"Experiment 1: Baseline locomotor activity in well habituated combined DAT/5-HT1B KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-16 02:54:00"}

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Relative Metric

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F1000Prime