Effects of ketamine treatment on cocaine-induced reinstatement and disruption of functional connectivity in unanesthetized rhesus monkeys.
Rationale: Substance use disorders are characterized by a loss of executive control over reward-based decision-making, and disruption of fronto-striatal connectivity has been implicated in this process. Sub-anesthetic ketamine has recently been shown to bolster fronto-striatal connectivity in drug-n...
| Publicado en: | Psychopharmacology Vol. 236; no. 7; pp. 2105 - 2119 |
|---|---|
| Autores principales: | , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Jul2019
|
| 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=137472324&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 137472324 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Jul2019 vid: 236 iid: 7 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 137472324 10.1007/s00213-019-05204-4 137472324 ppf: 2105 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Effects of ketamine treatment on cocaine-induced reinstatement and disruption of functional connectivity in unanesthetized rhesus monkeys. aug: au: Maltbie, Eric A. Gopinath, Kaundinya S. Howell, Leonard L. affil: Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd NE, 30329, Atlanta, GA, USA sug: ab: Rationale: Substance use disorders are characterized by a loss of executive control over reward-based decision-making, and disruption of fronto-striatal connectivity has been implicated in this process. Sub-anesthetic ketamine has recently been shown to bolster fronto-striatal connectivity in drug-naïve subjects. Objectives: The influence of ketamine treatment was examined on the disruptive effects of cocaine on functional connectivity (FC) and on cocaine-seeking behavior in female rhesus monkeys. Methods: Three female rhesus were trained for unanesthetized MRI scanning. Each received three drug-naïve/abstinent pharmacological MRI scans with acute injections of saline, cocaine (0.3 mg/kg i.v.), and cocaine (0.3 mg/kg i.v.) 48-h after a ketamine treatment (low dose = 0.345 mg/kg bolus + 0.256 mg/kg/h for 1 h; i.v.), and a fourth scan with saline injection following 2 months of daily cocaine self-administration. A separate cohort of five rhesus (4 female), all with extensive histories of cocaine exposure, underwent reinstatement testing 48 h after ketamine (or vehicle) treatment. Two sub-anesthetic doses were tested: low dose and high dose = 0.69 mg/kg + 0.512 mg/kg/h for 1 h. Results: Ketamine treatment attenuated the effects of cocaine on both global and fronto-striatal FC in drug-naïve/abstinent subjects. Two months of daily cocaine self-administration led to prolonged disruption of both global and fronto-striatal FC. Cocaine-seeking behavior during reinstatement was reduced following ketamine treatment at the low dose, but not high dose. Conclusion: These findings illustrate the disruptive effects of cocaine on functional connectivity and provide evidence for the potential efficacy of ketamine as a treatment for stimulant use disorder. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|