دورية أكاديمية
Exploring ketamine's reinforcement, cue-induced reinstatement, and nucleus accumbens cFos activation in male and female long evans rats.
| العنوان: | Exploring ketamine's reinforcement, cue-induced reinstatement, and nucleus accumbens cFos activation in male and female long evans rats. |
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| المؤلفون: | Hagarty DP; Department of Biomedical Sciences, College of Medicine, Program in Neuroscience, Florida State University, Tallahassee, FL, USA., Dawoud A; Department of Biomedical Sciences, College of Medicine, Program in Neuroscience, Florida State University, Tallahassee, FL, USA., Brea Guerrero A; Department of Biomedical Sciences, College of Medicine, Program in Neuroscience, Florida State University, Tallahassee, FL, USA., Phillips K; Department of Biomedical Sciences, College of Medicine, Program in Neuroscience, Florida State University, Tallahassee, FL, USA., Strong CE; Department of Biomedical Sciences, College of Medicine, Program in Neuroscience, Florida State University, Tallahassee, FL, USA., Jennings SD; Department of Biomedical Sciences, College of Medicine, Program in Neuroscience, Florida State University, Tallahassee, FL, USA., Crawford M; Department of Biomedical Sciences, College of Medicine, Program in Neuroscience, Florida State University, Tallahassee, FL, USA., Martinez K; Department of Biomedical Sciences, College of Medicine, Program in Neuroscience, Florida State University, Tallahassee, FL, USA., Csernecky O; Department of Biomedical Sciences, College of Medicine, Program in Neuroscience, Florida State University, Tallahassee, FL, USA., Saland SK; Department of Biomedical Sciences, College of Medicine, Program in Neuroscience, Florida State University, Tallahassee, FL, USA., Kabbaj M; Department of Biomedical Sciences, College of Medicine, Program in Neuroscience, Florida State University, Tallahassee, FL, USA. Electronic address: mkabbaj@fsu.edu. |
| المصدر: | Neuropharmacology [Neuropharmacology] 2024 Sep 01; Vol. 255, pp. 110008. Date of Electronic Publication: 2024 May 24. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Pergamon Press Country of Publication: England NLM ID: 0236217 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7064 (Electronic) Linking ISSN: 00283908 NLM ISO Abbreviation: Neuropharmacology Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Pergamon Press Original Publication: Oxford, New York, Pergamon. |
| مواضيع طبية MeSH: | Ketamine*/pharmacology , Ketamine*/administration & dosage , Nucleus Accumbens*/drug effects , Nucleus Accumbens*/metabolism , Cues* , Rats, Long-Evans* , Reinforcement, Psychology* , Dose-Response Relationship, Drug*, Animals ; Male ; Female ; Proto-Oncogene Proteins c-fos/metabolism ; Excitatory Amino Acid Antagonists/pharmacology ; Excitatory Amino Acid Antagonists/administration & dosage ; Rats ; Sex Characteristics ; Self Administration ; Conditioning, Operant/drug effects |
| مستخلص: | Ketamine (KET), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, has rapid onset of antidepressant effects in Treatment-Resistant Depression patients and repeated infusions are required to sustain its antidepressant properties. However, KET is an addictive drug, and so more preclinical and clinical research is needed to assess the safety of recurring treatments in both sexes. Thus, the aim of this study was to investigate the reinforcing properties of various doses of KET (0-, 0.125-, 0.25-, 0.5 mg/kg/infusion) and assess KET's cue-induced reinstatement and neuronal activation in both sexes of Long Evans rats. Neuronal activation was assessed using the protein expression of the immediate early gene cFos in the nucleus accumbens (Nac), an important brain area implicated in reward, reinforcement and reinstatement to most drug-related cues. Our findings show that KET has reinforcing effects in both male and female rats, albeit exclusively at the highest two doses (0.25 and 0.5 mg/kg/infusion). Furthermore, we noted sex differences, particularly at the highest dose of ketamine, with female rats displaying a higher rate of self-administration. Interestingly, all groups that self-administered KET reinstated to drug-cues. Following drug cue-induced reinstatement test in rats exposed to KET (0.25 mg/kg/infusion) or saline, there was higher cFos protein expression in KET-treated animals compared to saline controls, and higher cFos expression in the core compared to the shell subregions of the Nac. As for reinstatement, there were no notable sex differences reported for cFos expression in the Nac. These findings reveal some sex and dose dependent effects in KET's reinforcing properties and that KET at all doses induced similar reinstatement in both sexes. This study also demonstrated that cues associated with ketamine induce comparable neuronal activation in the Nac of both male and female rats. This work warrants further research into the potential addictive properties of KET, especially when administered at lower doses which are now being used in the clinic for treating various psychopathologies. Competing Interests: Declaration of competing interest The authors declare no competing financial interests. (Copyright © 2024 Elsevier Ltd. All rights reserved.) |
| معلومات مُعتمدة: | R01 DA043461 United States DA NIDA NIH HHS; R01 MH099085 United States MH NIMH NIH HHS |
| فهرسة مساهمة: | Keywords: Addiction; Dose-response; Relapse; Sex differences; cFos |
| المشرفين على المادة: | 690G0D6V8H (Ketamine) 0 (Proto-Oncogene Proteins c-fos) 0 (Excitatory Amino Acid Antagonists) |
| تواريخ الأحداث: | Date Created: 20240526 Date Completed: 20240606 Latest Revision: 20240606 |
| رمز التحديث: | 20240607 |
| DOI: | 10.1016/j.neuropharm.2024.110008 |
| PMID: | 38797243 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-7064 |
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| DOI: | 10.1016/j.neuropharm.2024.110008 |