Mu-opioid receptor knockout mice are more sensitive to chlordiazepoxide-induced anxiolytic behavior

Wang, Kuo-Ching; Lee, Yih-Jing; Fan, Lir‐Wan; Yang, Pao-Pao; Tao, Pao‐Luh; Ho, Ing-Kang; Tien, Lu-Tai

doi:10.1016/j.brainresbull.2012.10.009

Cited by 5 publications

(2 citation statements)

References 38 publications

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“…In agreement, corticosterone responses to stress were reduced in MOP knockouts revealing the facilitatory role of MOP in emotional responses to stress [171]. In spite of these emotional alterations, the anxiolytic-like effects of benzodiazepines were unaltered [172] or even enhanced [173] in MOP knockout mice, which could be related to an upregulation of the benzodiazepine receptor system in these mutants [174]. MOP knockouts also present an enhancement in 5-HT 1A receptor levels and reduction of M1 muscarinic receptors in several brain areas related to emotional behaviour control.…”

Section: Vesicular Monoamine Transporter (Vmat) Mutant Micesupporting

confidence: 53%

Genetically Modified Mice as Tools to Understand the Neurobiological Substrates of Depression

Robledo¹,

Martín‐García²,

Aso³

et al. 2014

CPD

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The pathophysiological mechanisms underlying depression are still poorly understood. An initial hypothesis postulated to explain the substrates of depression was based on the involvement of monoaminergic systems. This early theory was proposed from different findings obtained using pharmacological tools and can explain the mechanism of action of the drugs currently used to treat depression. However, more recent studies have revealed that other neurobiological processes different from monoamines also participate in the substrates of depression. These mechanisms include the participation of several neuromodulatory systems, stress-related circuits and neuroplastic changes that could represent a direct substrate for these pathophysiological processes. The lack of selective pharmacological tools for several of these potential targets of depression represents an important limitation to study their potential involvement. In the last two decades, different lines of genetically modified mice have been generated with selective deletions in specific genes related to the control of emotional responses. This review summarizes the main findings that have been obtained with these novel genetic tools to clarify the neurobiological substrates of depression. A particular focus has been devoted to the advances obtained with mice deficient in specific components of the monoaminergic, opioid and cannabinoid system and those with mutations in elements of the hypothalamic-pituitary-adrenal axis.

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Section: Vesicular Monoamine Transporter (Vmat) Mutant Micesupporting

confidence: 53%

Genetically Modified Mice as Tools to Understand the Neurobiological Substrates of Depression

Robledo¹,

Martín‐García²,

Aso³

et al. 2014

CPD

View full text Add to dashboard Cite

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“…The opioid pathway plays an important role in the modulation of anxiety, and activation of this pathway has been hypothesized to mediate anxiolytic responses [ 29 ]. For example, when the µ-opioid receptor agonist, endomorphine 1, was administered intracerebroventricularly into mice, an anxiolytic effect was observed in the EPM test [ 29 , 30 , 31 , 32 ]. Based on these findings and the results of the EPM assays conducted in the present study, it appears that the anxiolytic effect of PILAB 8 is mediated via µ-opioid receptors.…”

Section: Discussionmentioning

confidence: 99%

The Hypnotic, Anxiolytic, and Antinociceptive Profile of a Novel µ-Opioid Agonist

et al. 2017

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5′-4-Alkyl/aryl-1H-1,2,3-triazole derivatives PILAB 1–12 were synthesized and a pharmacological screening of these derivatives was performed to identify a possible effect on the Central Nervous System (CNS) and to explore the associated mechanisms of action. The mice received a peritoneal injection (100 µmol/kg) of each of the 12 PILAB derivatives 10 min prior to the injection of pentobarbital and the mean hypnosis times were recorded. The mean hypnosis time increased for the mice treated with PILAB 8, which was prevented when mice were administered CTOP, a µ-opioid antagonist. Locomotor and motor activities were not affected by PILAB 8. The anxiolytic effect of PILAB 8 was evaluated next in an elevated-plus maze apparatus. PILAB 8 and midazolam increased a percentage of entries and spent time in the open arms of the apparatus compared with the control group. Conversely, a decrease in the percentages of entries and time spent in the closed arms were observed. Pretreatment with naloxone, a non-specific opioid antagonist, prior to administration of PILAB 8 exhibited a reverted anxiolytic effect. PILAB 8 exhibited antinociceptive activity in the hot plate test, and reduced reactivity to formalin in the neurogenic and the inflammatory phases. These data suggest that PILAB 8 can activate µ-opioid receptors to provoke antinociceptive and anti-inflammatory effects in mice.

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The Role of miR-150 in Stress-Induced Anxiety-Like Behavior in Mice

et al. 2018

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Stress plays a crucial role in several psychiatric disorders, including anxiety. However, the underlying mechanisms remain poorly understood. Here, we used acute stress (AS) and chronic restraint stress (CRS) models to develop anxiety-like behavior and investigate the role of miR-150 in the hippocampi of mice. Corticosterone levels as well as glutamate receptors in the hippocampus were evaluated. We found that anxiety-like behavior was induced after either AS or CRS, as determined by the open-field test (OFT) and elevated plus-maze test (EPM). Increased corticosterone levels were observed in the blood of AS and CRS groups, while the expression of miR-150 mRNA in the hippocampus was significantly decreased. The expressions of GluN2A, GluR1, GluR2, and V-Glut2 in the hippocampus were decreased after either AS or CRS. Hippocampal GAD67 expression was increased by AS but not CRS, and GluN2B expression was decreased by CRS but not AS. Adult miR-150 knockout mice showed anxiety-like behavior, as assessed by the OFT and EPM. The expressions of GluN2A, GluN2B, GluR1, and GluR2 were also downregulated, but the expression of V-Glut2 was upregulated in the hippocampi of miR-150 knockout mice compared with wild-type mice. Interestingly, we found that the miR-150 knockout mice showed decreased dendrite lengths, dendrite branchings, and numbers of dendrite spines in the hippocampus compared with wild-type mice. These results suggest that miR-150 may influence the synaptic plasticity of the hippocampus and play a significant role in stress-induced anxiety-like behavior in adult mice.

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Mu-opioid receptor knockout mice are more sensitive to chlordiazepoxide-induced anxiolytic behavior

Cited by 5 publications

References 38 publications

Genetically Modified Mice as Tools to Understand the Neurobiological Substrates of Depression

Genetically Modified Mice as Tools to Understand the Neurobiological Substrates of Depression

The Hypnotic, Anxiolytic, and Antinociceptive Profile of a Novel µ-Opioid Agonist

The Role of miR-150 in Stress-Induced Anxiety-Like Behavior in Mice

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