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Individual differences in the effects of midazolam on anxiety-like behavior, learning, reward, and choice behavior in male mice.

التفاصيل البيبلوغرافية
العنوان: Individual differences in the effects of midazolam on anxiety-like behavior, learning, reward, and choice behavior in male mice.
المؤلفون: Jovita-Farias C; Department of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil., Follett ME; Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, United States., Dias-Junior BC; Department of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil., Serra YA; Department of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil., Kisaki ND; Department of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil., Barros-Santos T; Department of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil., de Jesus NMS; Department of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil., Rodrigues IRS; Department of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil., Macedo LEL; Department of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil., Malpezzi-Marinho ELA; Department of Biological Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil., Oliveira-Lima AJ; Department of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil., Marinho EAV; Department of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil., Rowlett JK; Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, United States., Berro LF; Department of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil.; Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, United States.
المصدر: Frontiers in psychiatry [Front Psychiatry] 2023 Mar 03; Vol. 14, pp. 1122568. Date of Electronic Publication: 2023 Mar 03 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101545006 Publication Model: eCollection Cited Medium: Print ISSN: 1664-0640 (Print) Linking ISSN: 16640640 NLM ISO Abbreviation: Front Psychiatry Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Switzerland : Frontiers Research Foundation, 2010-
مستخلص: Introduction: The aim of the present study was to investigate the behavioral effects of the benzodiazepine midazolam in male mice, in models of anxiolysis, learning, and abuse-related effects.
Methods: In a first set of experiments, male Swiss mice were submitted to the training session of a discriminative avoidance (DA) task on the elevated plus maze to evaluate anxiety-like behavior and learning after vehicle or midazolam (1, 2 or 5 mg/kg, i.g.) administration. The same animals were submitted to a conditioned place preference (CPP) protocol with midazolam (1, 2 or 5 mg/kg, i.g.). In a second experiment, outbred (Swiss) and inbred (C57BL/6) male mice were submitted to a two-bottle choice (TBC) oral midazolam drinking procedure. Animals were exposed to one sucrose bottle and one midazolam (0.008, 0.016 or 0.032 mg/ml) plus sucrose bottle.
Results: Midazolam (1 and 2 mg/kg) induced anxiolytic-like effects, and all doses of midazolam prevented animals from learning to avoid the aversive closed arm during the DA training session. Assessment of midazolam reward via the CPP procedure and choice via the TBC procedure showed notable variability. A 2-step cluster analysis for the CPP data showed that midazolam data were well-fitted to 2 separate clusters (preference vs. aversion), albeit with the majority of mice showing preference (75%). Correlational and regression analyses showed no relationship between midazolam reward and anxiolytic-like effects (time spent in the open arms in the DA test) or learning/memory. Two-step cluster analysis of the TBC data also demonstrated that, regardless of strain, mice overall fell into two clusters identified as midazolam-preferring or midazolam-avoiding groups. Both midazolam preference and avoidance were concentration-dependent in a subset of mice.
Discussion: Our findings show that midazolam preference is a multifactorial behavior, and is not dependent solely on the emergence of therapeutic (anxiolytic-like) effects, learning impairments, or on genetic factors (inbred vs. outbred animals).
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Jovita-Farias, Follett, Dias-Junior, Serra, Kisaki, Barros-Santos, de Jesus, Rodrigues, Macedo, Malpezzi-Marinho, Oliveira-Lima, Marinho, Rowlett and Berro.)
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معلومات مُعتمدة: R01 DA011792 United States DA NIDA NIH HHS; R01 DA043204 United States DA NIDA NIH HHS
فهرسة مساهمة: Keywords: benzodiazepine; conditioned place preference; elevated plus maze; mice; midazolam; self-administration
تواريخ الأحداث: Date Created: 20230320 Latest Revision: 20240104
رمز التحديث: 20240104
مُعرف محوري في PubMed: PMC10021295
DOI: 10.3389/fpsyt.2023.1122568
PMID: 36937711
قاعدة البيانات: MEDLINE
الوصف
تدمد:1664-0640
DOI:10.3389/fpsyt.2023.1122568