Clozapine counteracts a ketamine-induced depression of hippocampal-prefrontal neuroplasticity and alters signaling pathway phosphorylation
Publication Date
May 04, 2017
Authors
Marion Rame, Dorian Caudal, Esther Schenker, Per Svenningsson, et al
Volume
12
Issue
5
Pages
e0177036
DOI
https://dx.plos.org/10.1371/journal.pone.0177036
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0177036
Scopus
85019068155
Mendeley
http://www.mendeley.com/research/clozapine-counteracts-ketamineinduced-depression-hippocampalprefrontal-neuroplasticity-alters-signal
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Mendeley | Further Information

{"title"=>"Clozapine counteracts a ketamine-induced depression of hippocampal-prefrontal neuroplasticity and alters signaling pathway phosphorylation", "type"=>"journal", "authors"=>[{"first_name"=>"Marion", "last_name"=>"Rame", "scopus_author_id"=>"56305153900"}, {"first_name"=>"Dorian", "last_name"=>"Caudal", "scopus_author_id"=>"37021210600"}, {"first_name"=>"Esther", "last_name"=>"Schenker", "scopus_author_id"=>"55471589900"}, {"first_name"=>"Per", "last_name"=>"Svenningsson", "scopus_author_id"=>"7004099018"}, {"first_name"=>"Michael", "last_name"=>"Spedding", "scopus_author_id"=>"7005213217"}, {"first_name"=>"Therèse M.", "last_name"=>"Jay", "scopus_author_id"=>"7003597249"}, {"first_name"=>"Bill P.", "last_name"=>"Godsil", "scopus_author_id"=>"6505932205"}], "year"=>2017, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"28472198", "sgr"=>"85019068155", "doi"=>"10.1371/journal.pone.0177036", "scopus"=>"2-s2.0-85019068155", "pui"=>"615955968", "isbn"=>"1111111111", "issn"=>"19326203"}, "id"=>"00efac4f-34f9-3144-aca7-aa6a63ca967c", "abstract"=>"Single sub-anesthetic doses of ketamine can exacerbate the symptoms of patients diagnosed with schizophrenia, yet similar ketamine treatments rapidly reduce depressive symptoms in major depression. Acute doses of the atypical antipsychotic drug clozapine have also been shown to counteract ketamine-induced psychotic effects. In the interest of understanding whether these drug effects could be modeled with alterations in neuroplasticity, we examined the impact of acutely-administered ketamine and clozapine on in vivo long-term potentiation (LTP) in the rat's hippocampus-to-prefrontal cortex (H-PFC) pathway. We found that a low dose of ketamine depressed H-PFC LTP, whereas animals that were co-administrated the two drugs displayed LTP that was similar to a saline-treated control. To address which signaling molecules might mediate such effects, we also examined phosphorylation and total protein levels of GSK3beta, GluA1, TrkB, ERK, and mTOR in prefrontal and hippocampal sub-regions. Among the statistically significant effects that were detected (a) both ketamine and clozapine increased the phosphorylation of Ser9-GSK3beta throughout the prefrontal cortex and of Ser2481-mTOR in the dorsal hippocampus (DH), (b) clozapine increased the phosphorylation of Ser831-GluA1 throughout the prefrontal cortex and of Ser845-GluA1 in the ventral hippocampus, (c) ketamine treatment increased the phosphorylation of Thr202/Tyr204-ERK in the medial PFC (mPFC), and (d) clozapine treatment was associated with decreases in the phosphorylation of Tyr705-TrkB in the DH and of Try816-TrkB in the mPFC. Further analyses involving phosphorylation effect sizes also suggested Ser831-GluA1 in the PFC displayed the highest degree of clozapine-responsivity relative to ketamine. These results provide evidence for how ketamine and clozapine treatments affect neuroplasticity and signaling pathways in the stress-sensitive H-PFC network. They also demonstrate the potential relevance of H-PFC pathway neuroplasticity for modeling ketamine-clozapine interactions in regards to psychosis.", "link"=>"http://www.mendeley.com/research/clozapine-counteracts-ketamineinduced-depression-hippocampalprefrontal-neuroplasticity-alters-signal", "reader_count"=>15, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>3, "Medicine and Dentistry"=>2, "Neuroscience"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Immunology and Microbiology"=>1, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Canada"=>1}, "group_count"=>0}

Scopus | Further Information

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