Ketamine induces immediate and delayed alterations of OCD-like behavior.

Rationale: Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by intrusive obsessive thoughts and/or compulsive behaviors. Currently, serotonin reuptake inhibitors (SRIs) provide the only pharmacological monotherapy for OCD, but response rates are insufficient. Ketamine, a n...

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Publicado en:Psychopharmacology Vol. 237; no. 3; pp. 627 - 639
Autores principales: Thompson, Summer L., Welch, Amanda C., Iourinets, Julia, Dulawa, Stephanie C.
Formato: Journal Article
Publicado: Springer Nature Mar2020
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Mar2020
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      pub: Springer Nature
      place: New York, New York
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        141881029
        10.1007/s00213-019-05397-8
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        atl: Ketamine induces immediate and delayed alterations of OCD-like behavior.
      aug:
        au:
          Thompson, Summer L.
          Welch, Amanda C.
          Iourinets, Julia
          Dulawa, Stephanie C.
        affil: Committee on Neurobiology, University of Chicago, 60637, Chicago, IL, USA
      sug:
      ab: Rationale: Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by intrusive obsessive thoughts and/or compulsive behaviors. Currently, serotonin reuptake inhibitors (SRIs) provide the only pharmacological monotherapy for OCD, but response rates are insufficient. Ketamine, a noncompetitive NMDA receptor antagonist, was reported to have rapid, sustained therapeutic effects in OCD patients. However, the mechanisms remain unknown. Objectives: Here, we aimed to provide a platform for investigating mechanisms underlying anti-OCD effects of ketamine treatment by assessing whether ketamine pretreatment could alleviate 5-HT1B receptor (5-HT1BR)-induced OCD-like behavior in mice. Methods: We assessed whether acute ketamine (0, 3, 10, 30 mg/kg), administered at two pretreatment time points (30 min, 24 h), would modulate 5-HT1BR-induced OCD-like behavior in mice. Behavioral measures were perseverative hyperlocomotion in the open field and deficits in prepulse inhibition (PPI) induced by acute pharmacological 5-HT1BR challenge. Results: Three milligrams per kilogram of ketamine reduced 5-HT1BR-induced perseverative hyperlocomotion, but not PPI deficits, 24 h postinjection. In contrast, higher doses of ketamine were either ineffective (10 mg/kg) or exacerbated (30 mg/kg) 5-HT1BR-induced perseverative hyperlocomotion 30 min postinjection. At 24 h postinjection, 30 mg/kg ketamine reduced perseverative hyperlocomotion across all groups. Conclusions: Our results suggest that the 5-HT1BR-induced model of OCD-like behavior is sensitive to a low dose of ketamine, a potential fast-acting anti-OCD treatment, and may provide a tool for studying mechanisms underlying the rapid therapeutic effects of ketamine in OCD patients.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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