Ketamine-induced brain activation in awake female nonhuman primates: a translational functional imaging model.
Rationale: There is significant interest in the NMDA receptor antagonist ketamine due to its efficacy in treating depressive disorders and its induction of psychotic-like symptoms that make it a useful tool for modeling psychosis. Objective: The present study extends the successful development of an...
| Publicado en: | Psychopharmacology Vol. 233; no. 6; pp. 961 - 973 |
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| Autores principales: | , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Mar2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=113139784&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 113139784 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Mar2016 vid: 233 iid: 6 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 113139784 10.1007/s00213-015-4175-8 113139784 ppf: 961 ppct: 12 formats: fmt: @attributes: type: P tig: atl: Ketamine-induced brain activation in awake female nonhuman primates: a translational functional imaging model. aug: au: Maltbie, Eric Gopinath, Kaundinya Urushino, Naoko Kempf, Doty Howell, Leonard affil: Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd NE Atlanta 30329 USA sug: ab: Rationale: There is significant interest in the NMDA receptor antagonist ketamine due to its efficacy in treating depressive disorders and its induction of psychotic-like symptoms that make it a useful tool for modeling psychosis. Objective: The present study extends the successful development of an apparatus and methodology to conduct pharmacological MRI studies in awake rhesus monkeys in order to evaluate the CNS effects of ketamine. Methods: Functional MRI scans were conducted in four awake adult female rhesus monkeys during sub-anesthetic intravenous (i.v.) infusions of ketamine (0.345 mg/kg bolus followed by 0.256 mg/kg/h constant infusion) with and without risperidone pretreatment (0.06 mg/kg). Statistical parametric maps of ketamine-induced blood oxygenation level-dependent (BOLD) activation were obtained with appropriate general linear regression models (GLMs) incorporating motion and hemodynamics of ketamine infusion. Results: Ketamine infusion induced and sustained robust BOLD activation in a number of cortical and subcortical regions, including the thalamus, cingulate gyrus, and supplementary motor area. Pretreatment with the antipsychotic drug risperidone markedly blunted ketamine-induced activation in many brain areas. Conclusions: The results are remarkably similar to human imaging studies showing ketamine-induced BOLD activation in many of the same brain areas, and pretreatment with risperidone or another antipsychotic blunting the ketamine response to a similar extent. The strong concordance of the functional imaging data in humans with these results from nonhuman primates highlights the translational value of the model and provides an excellent avenue for future research examining the CNS effects of ketamine. This model may also be a useful tool for evaluating the efficacy of novel antipsychotic drugs. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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