The Metabotropic Glutamate 5 Receptor Modulates Extinction and Reinstatement of Methamphetamine-Seeking in Mice
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{"title"=>"The Metabotropic Glutamate 5 Receptor Modulates Extinction and Reinstatement of Methamphetamine-Seeking in Mice", "type"=>"journal", "authors"=>[{"first_name"=>"Rose", "last_name"=>"Chesworth", "scopus_author_id"=>"34979866800"}, {"first_name"=>"Robyn M.", "last_name"=>"Brown", "scopus_author_id"=>"36016131300"}, {"first_name"=>"Jee Hyun", "last_name"=>"Kim", "scopus_author_id"=>"57192574680"}, {"first_name"=>"Andrew J.", "last_name"=>"Lawrence", "scopus_author_id"=>"34870137500"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84879822167", "sgr"=>"84879822167", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0068371", "pmid"=>"23861896", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"369260792"}, "id"=>"39519539-2bf9-31a6-8c54-3abfc7e5fea6", "abstract"=>"Methamphetamine (METH) is a highly addictive psychostimulant with no therapeutics registered to assist addicts in discontinuing use. Glutamatergic dysfunction has been implicated in the development and maintenance of addiction. We sought to assess the involvement of the metabotropic glutamate 5 receptor (mGlu5) in behaviours relevant to METH addiction because this receptor has been implicated in the actions of other drugs of abuse, including alcohol, cocaine and opiates. mGlu5 knockout (KO) mice were tested in intravenous self-administration, conditioned place preference and locomotor sensitization. Self-administration of sucrose was used to assess the response of KO mice to a natural reward. Acquisition and maintenance of self-administration, as well as the motivation to self-administer METH was intact in mGlu5 KO mice. Importantly, mGlu5 KO mice required more extinction sessions to extinguish the operant response for METH, and exhibited an enhanced propensity to reinstate operant responding following exposure to drug-associated cues. This phenotype was not present when KO mice were tested in an equivalent paradigm assessing operant responding for sucrose. Development of conditioned place preference and locomotor sensitization were intact in KO mice; however, conditioned hyperactivity to the context previously paired with drug was elevated in KO mice. These data demonstrate a role for mGlu5 in the extinction and reinstatement of METH-seeking, and suggests a role for mGlu5 in regulating contextual salience.", "link"=>"http://www.mendeley.com/research/metabotropic-glutamate-5-receptor-modulates-extinction-reinstatement-methamphetamineseeking-mice", "reader_count"=>36, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>2, "Student > Master"=>3, "Student > Bachelor"=>6, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>2, "Student > Master"=>3, "Student > Bachelor"=>6, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>11, "Medicine and Dentistry"=>4, "Neuroscience"=>7, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Business, Management and Accounting"=>1, "Psychology"=>6}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>7}, "Psychology"=>{"Psychology"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>1, "United Kingdom"=>1, "South Africa"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1112298"], "description"=>"<p><b>A)</b> Average active lever presses during Stable FR1 and the final 2 days of extinction. Both genotypes significantly decreased their active lever presses during both days of extinction. <b>B)</b> Average active lever presses during extinction and cue-induced reinstatement. Both genotypes increased their active lever pressing in the reinstatement test following extinction. Data (mean±SEM) analysed using two-way RM ANOVA, followed by one-way ANOVA split by the factor ‘genotype’ with a Bonferroni correction. Significant effects of ‘day’ (<i>vs.</i> Stable FR1) are represented by “#” (<sup>##</sup><i>p</i><.01; <sup>###</sup><i>p</i><.001). Abbreviations: EXT - final extinction score; FR1– fixed ratio 1; Reinst - reinstatement.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Biochemistry", "Neurochemistry", "neuroscience", "Neurochemicals", "glutamate", "Mental health", "psychiatry", "reinstatement", "operant"], "article_id"=>740389, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rose Chesworth", "Robyn M. Brown", "Jee Hyun Kim", "Andrew J. Lawrence"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0068371.g004", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Extinction_and_reinstatement_of_the_operant_response_for_sucrose_/740389", "title"=>"Extinction and reinstatement of the operant response for sucrose.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 03:07:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/1112299"], "description"=>"<p>Stable FR1 infusions averaged over 5 days of stable self-administration; extinction data averaged over the final two days of extinction. Data presented as means±SEM. Data analysed using two- or three-way RM ANOVA, followed by one-way ANOVA split by corresponding factor, where appropriate. Significant effects of ‘lever type’ are indicated by hash symbols (<i>vs</i>. inactive lever; <sup>##</sup><i>p</i><.01, <sup>###</sup><i>p</i><.001); significant effects of ‘genotype’ are indicated by asterisks (*<i>p</i><.05); significant effects of ‘day’ are indicated by ‘$’ (<sup>$</sup><i>p</i><.05). Abbreviations: ALP - active lever press; FR1 - fixed ratio 1; ILP - inactive lever press.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Biochemistry", "Neurochemistry", "neuroscience", "Neurochemicals", "glutamate", "Mental health", "psychiatry", "responses", "infusions", "meth", "ivsa", "fr1", "extinction"], "article_id"=>740390, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rose Chesworth", "Robyn M. Brown", "Jee Hyun Kim", "Andrew J. Lawrence"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0068371.t001", "stats"=>{"downloads"=>4, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lever_Responses_and_Infusions_during_METH_IVSA_FR1_Acquisition_Self_administration_Extinction_and_Reinstatement_/740390", "title"=>"Lever Responses and Infusions during METH IVSA FR1 Acquisition, Self-administration, Extinction and Reinstatement.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-07-04 03:07:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/1112296"], "description"=>"<p><b>A)</b> Self-administration of 10% sucrose solution with a fixed ratio 1 schedule in WT and mGlu5 KO mice. Single lever training (days 1–3) was followed by double lever training (days 4–8). A significant main effect of ‘lever type’ suggests clear discrimination for the active lever in each genotype<b>. B)</b> Acquisition and stable self-administration of 3 µg/kg/infusion METH in WT and mGlu5 KO mice. <b>C)</b> Final breakpoint reached within a two-hour test using a progressive ratio schedule of reinforcement. Data (mean±SEM) analysed using two- or three-way RM ANOVA, followed by one-way ANOVA split by the factor ‘genotype’ with a Bonferroni correction where appropriate. Significant main effects of ‘lever type’ during sucrose and METH acquisition and self-administration suggest clear discrimination for the active lever in each genotype.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Biochemistry", "Neurochemistry", "neuroscience", "Neurochemicals", "glutamate", "Mental health", "psychiatry", "meth", "self-administration"], "article_id"=>740387, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rose Chesworth", "Robyn M. Brown", "Jee Hyun Kim", "Andrew J. Lawrence"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0068371.g002", "stats"=>{"downloads"=>8, "page_views"=>126, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Instrumental_learning_METH_self_administration_and_progressive_ratio_testing_/740387", "title"=>"Instrumental learning, METH self-administration and progressive ratio testing.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 03:07:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/1112297"], "description"=>"<p><b>A)</b> Percentage of mice extinguished per day. mGlu5 KO mice took a significantly greater number of days to extinguish the operant response. Data (mean±SEM) analysed using a log-rank test; there was a significant effect of ‘genotype’ (<i>p</i> = .03). <b>B)</b> Average number of days to extinguish the operant response. mGlu5 KO mice took significantly longer to extinguish their operant responding than WTs. Data (mean±SEM) analysed using one-way ANOVA; a significant effect of ‘genotype’ indicated by ‘*’ (*<i>p</i><.05). <b>C)</b> Active lever pressing during reinstatement. Data (mean±SEM) analysed using one-way ANOVA. <b>D)</b> Proportion of WT and mGlu5 KO mice meeting reinstatement criteria. Data analysed using a Fisher’s exact test. Abbreviations: Reinst - mice which met reinstatement criteria; No Reinst - mice which did not meet reinstatement criteria.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Biochemistry", "Neurochemistry", "neuroscience", "Neurochemicals", "glutamate", "Mental health", "psychiatry", "reinstatement", "operant"], "article_id"=>740388, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rose Chesworth", "Robyn M. Brown", "Jee Hyun Kim", "Andrew J. Lawrence"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0068371.g003", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Extinction_and_reinstatement_of_the_operant_response_for_METH_/740388", "title"=>"Extinction and reinstatement of the operant response for METH.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 03:07:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/1112295"], "description"=>"<p><b>A)</b> Preference score in WT and mGlu5 KO mice at habituation and test. Preference score is defined as (time spent in the METH-paired compartment – time spent in the saline-paired compartment). <b>B)</b> Locomotor sensitization in WT and mGlu5 KO mice following acute saline or 2 mg/kg METH i.p. injection over 4 consecutive days. <b>C)</b> Conditioned hyperactivity in WT and mGlu5 KO mice during the CPP test. Data (mean±SEM) analysed using two- or three-way RM ANOVA, followed by one-way ANOVA split by the factor ‘genotype’ with a Bonferroni correction. In Figs <b>A)</b> and <b>C)</b>, significant effects of ‘day’ (<i>vs.</i> habituation) are represented by “#” (<sup>###</sup><i>p</i><.001); significant effects of ‘genotype’ (<i>vs</i>. WT on the same day) are represented by ‘*’ (**<i>p</i><.01). In Fig <b>B)</b>, significant effects of ‘day’ (vs. METH day 1) are indicated by ‘$’ for WT mice (<sup>$$$</sup><i>p</i><.001), ‘#’ for mGlu5 KO mice (<sup>###</sup><i>p</i><.001). Significant effects of ‘day’ (vs. saline day 1) are indicated by ‘*’ for WT mice (***<i>p</i><.001) and ‘?’ for mGlu5 KO mice (???<i>p</i><.001). A significant ‘day’ × ‘genotype’ interaction was present in both Fig. A) and C), suggesting <b>A)</b> a greater change degree of change from habituation to test in WT compared to mGlu5 KO mice, and <b>C)</b> a greater change degree of change from habituation to test in mGlu5 KO compared to WT mice. Abbreviations: Saline 1 - day 1 of saline treatment.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Biochemistry", "Neurochemistry", "neuroscience", "Neurochemicals", "glutamate", "Mental health", "psychiatry", "cpp", "locomotor", "sensitization", "conditioned"], "article_id"=>740386, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rose Chesworth", "Robyn M. Brown", "Jee Hyun Kim", "Andrew J. Lawrence"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0068371.g001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_METH_CPP_Preference_Score_Locomotor_Sensitization_and_Conditioned_Hyperactivity_/740386", "title"=>"METH CPP Preference Score, Locomotor Sensitization and Conditioned Hyperactivity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 03:07:59"}

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  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[266, 468, 593, 703, 804, 903, 993, 1084, 1171, 1256, 1339, 1422, 1492]}, {"subject_area"=>"/Biology and life sciences/Neuroscience", "average_usage"=>[261, 444, 554, 655, 748, 834, 923, 1004, 1089, 1170, 1244, 1315, 1380]}, {"subject_area"=>"/Biology and life sciences/Physiology", "average_usage"=>[256, 449, 572, 676, 775, 866, 955, 1041, 1127, 1213, 1290, 1370, 1437]}, {"subject_area"=>"/Biology and life sciences/Psychology", "average_usage"=>[284, 458, 579, 688, 782, 879, 957, 1048, 1126, 1204, 1280, 1357, 1415]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[264, 460, 584, 692, 794, 887, 978, 1067, 1154, 1241, 1328, 1408, 1474]}, {"subject_area"=>"/Medicine and health sciences/Pharmacology", "average_usage"=>[265, 471, 604, 723, 827, 926, 1022, 1113, 1210, 1290, 1377, 1454, 1532]}, {"subject_area"=>"/Physical sciences/Chemistry", "average_usage"=>[247, 429, 544, 647, 747, 842, 929, 1012, 1099, 1179, 1263, 1339, 1409]}, {"subject_area"=>"/Physical sciences/Mathematics", "average_usage"=>[259, 431, 541, 639, 727, 816, 898, 980, 1061, 1136, 1214, 1294, 1356]}, {"subject_area"=>"/Social sciences", "average_usage"=>[289, 475, 593, 703, 805, 902, 990, 1078, 1158, 1250, 1336, 1417, 1482]}]}
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