Chronic MAP4343 reverses escalated alcohol drinking in a mouse model of alcohol use disorder DOI Creative Commons
Giovana C. Macedo, Max Kreifeldt, Scott P. Goulding

et al.

Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 20, 2023

Abstract Alcohol use disorders can be driven by negative reinforcement. Alterations of the microtubule cytoskeleton have been associated with mood regulation in context depression. Notably, MAP4343, a pregnenolone derivative known to promote tubulin assembly, has antidepressant properties. In present study, we tested hypothesis that MAP4343 may reduce excessive alcohol drinking mouse model dependence normalizing affect during withdrawal. Adult male C57BL/6J mice were given limited access voluntary and ethanol intake escalation was induced chronic intermittent (CIE) vapor inhalation. Chronic, but not acute, administration reduced this effect more pronounced CIE-exposed mice. There complex interaction between effects on affective behaviors. elevated plus maze, tended increase open-arm exploration alcohol-naive it alcohol-withdrawn tail suspension test, immobility selectively Air-exposed alcohol-drinking Finally, countered plasma corticosterone reduction CIE. Parallel analysis post-translational modifications revealed lower α-tubulin acetylation medial prefrontal cortex CIE-withdrawn Altogether, these data support relevance microtubules as therapeutic target for treatment AUD.

Language: Английский

KCa2 channel positive modulation reduces alcohol drinking in female C57BL/6J mice DOI

Kerstin Lindquist,

Audrey E. Padula,

Natalie S Katzenmeyer

et al.

Alcohol, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Chronic alcohol induced mechanical allodynia by promoting neuroinflammation: A mouse model of alcohol‐evoked neuropathic pain DOI Creative Commons
Vittoria Borgonetti, Amanda J. Roberts, Michal Bajo

et al.

British Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 180(18), P. 2377 - 2392

Published: April 13, 2023

Abstract Background and Purpose Chronic pain is considered a key factor contributing to alcohol use disorder (AUD). The mechanisms responsible for chronic associated with consumption are unknown. We evaluated the development of in mouse model dependence investigate role neuroinflammation. Experimental Approach chronic‐intermittent ethanol two‐bottle choice CIE‐2BC paradigm generates three groups: alcohol‐dependent escalating intake, nondependent (moderate drinking) alcohol‐naïve control male female mice. measured mechanical allodynia during withdrawal after last voluntary drinking. Immunoblotting was used evaluate protein levels IBA‐1, CSFR, IL‐6, p38 ERK2/1 spinal cord tissue dependent non‐dependent animals. Key Results found significant escalation drinking group compared group. developed 72 h withdrawal, which completely reversed observed an increased hypersensitivity naïve 50% Increased IBA‐1 CSFR expression both hypersensitivity‐abstinence related neuropathy‐alcohol mice, IL‐6 ERK1/2 activation mice hypersensitivity‐related abstinence, but not alcohol‐evoked neuropathic pain. Conclusions Implications induces two distinct conditions specific type exposure: abstinence‐related about half

Language: Английский

Citations

19
VGluT2 neuron subtypes in the paraventricular thalamic nucleus regulate depression in paraquat-induced Parkinson’s disease DOI
Yu Zhang,

Yihua Jiang,

Zhen Yu

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 472, P. 134559 - 134559

Published: May 9, 2024

Language: Английский

Citations

4
The link between early-life adversity and later alcohol use disorder: a role for microglia? DOI Creative Commons

H Lichtenstein,

Michelle K. Sequeira, Jessica L. Bolton

et al.

Neurobiology of Stress, Journal Year: 2025, Volume and Issue: unknown, P. 100714 - 100714

Published: Feb. 1, 2025

Language: Английский

Citations

0
Histone deacetylase inhibitor decreases hyperalgesia in a mouse model of alcohol withdrawal‐induced hyperalgesia DOI Creative Commons

Jhoan Aguilar,

Luana Martins de Carvalho, Hu Chen

et al.

Alcohol Clinical and Experimental Research, Journal Year: 2024, Volume and Issue: 48(3), P. 478 - 487

Published: Feb. 20, 2024

Abstract Background Alcohol withdrawal‐induced hyperalgesia (AWH) is characterized as an increased pain sensitivity observed after cessation of chronic alcohol use. can contribute to the negative affective state associated with abstinence and increase susceptibility relapse. We aimed characterize in mice during withdrawal from two different models exposure: drinking dark (DID) Lieber–DeCarli liquid diet. also investigated whether treatment a histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), could ameliorate AWH treated Methods Male female C57BL/6J were used for these studies. In DID model, received bottles 20% ethanol or water cycle 4 h per day on four consecutive days week 6 weeks. Peripheral mechanical was measured weekly morning Day 5 using von Frey filaments. (5% v/v) control diet 10 days, along single binge gavage (5 g/kg) gavage, respectively, 10. administration at 24 72 into withdrawal. An independent group that administered SAHA (50 mg/kg, i.p.) Results exhibited hypersensitivity consuming weeks procedure. led both sexes. Suberoylanilide alleviated AWH. Conclusions These results demonstrate males Like previous findings rats, HDAC inhibition reduced mice, suggesting epigenetic mechanisms are involved

Language: Английский

Citations

2
Impact of Elevated Brain IL-6 in Transgenic Mice on the Behavioral and Neurochemical Consequences of Chronic Alcohol Exposure DOI Creative Commons
Donna L. Gruol,

Delilah Calderon,

Salvador Huitrón‐Reséndiz

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(18), P. 2306 - 2306

Published: Sept. 19, 2023

Alcohol consumption activates the neuroimmune system of brain, a in which brain astrocytes and microglia play dominant roles. These glial cells normally produce low levels factors, are important signaling factors regulators function. activation is known to dysregulate production such as cytokine IL-6, thereby changing status could impact actions alcohol. The consequences neuroimmune-alcohol interactions not fully known. In current studies we investigated this issue transgenic (TG) mice with altered relative IL-6. TG express elevated astrocyte-produced condition occur alcohol exposure. Standard behavioral tests drinking negative affect/emotionality were carried out homozygous heterozygous control assess on chronic intermittent (ethanol) (CIE) exposure these behaviors. expressions signal transduction synaptic proteins also assessed by Western blot identify alcohol-neuroimmune neurochemistry. results from show that respect IL-6 significantly impacts effects multiple levels.

Language: Английский

Citations

5
Chronic MAP4343 reverses escalated alcohol drinking in a mouse model of alcohol use disorder DOI Creative Commons
Giovana C. Macedo, Max Kreifeldt, Scott P. Goulding

et al.

Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 20, 2023

Abstract Alcohol use disorders can be driven by negative reinforcement. Alterations of the microtubule cytoskeleton have been associated with mood regulation in context depression. Notably, MAP4343, a pregnenolone derivative known to promote tubulin assembly, has antidepressant properties. In present study, we tested hypothesis that MAP4343 may reduce excessive alcohol drinking mouse model dependence normalizing affect during withdrawal. Adult male C57BL/6J mice were given limited access voluntary and ethanol intake escalation was induced chronic intermittent (CIE) vapor inhalation. Chronic, but not acute, administration reduced this effect more pronounced CIE-exposed mice. There complex interaction between effects on affective behaviors. elevated plus maze, tended increase open-arm exploration alcohol-naive it alcohol-withdrawn tail suspension test, immobility selectively Air-exposed alcohol-drinking Finally, countered plasma corticosterone reduction CIE. Parallel analysis post-translational modifications revealed lower α-tubulin acetylation medial prefrontal cortex CIE-withdrawn Altogether, these data support relevance microtubules as therapeutic target for treatment AUD.

Language: Английский

Citations

4