Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2024, Volume and Issue: unknown, P. 111232 - 111232
Published: Dec. 1, 2024
Language: Английский
Pharmacological Research, Journal Year: 2024, Volume and Issue: 207, P. 107312 - 107312
Published: July 18, 2024
Addiction is a chronic relapsing disease with high morbidity and mortality. Treatments for addiction include pharmacological psychosocial interventions; however, currently available medications are limited in number efficacy. The glucagon-like-peptide-1 (GLP-1) system emerging as potential novel pharmacotherapeutic target alcohol other substance use disorders (ASUDs). In this review, we summarize discuss the wealth of evidence from testing GLP-1 receptor (GLP-1R) agonist preclinical models humans ASUDs, possible mechanisms underlying impact GLP-1R agonists on alcohol/substance use, gaps knowledge, future directions. Most research has been conducted relation to use; psychostimulants, opioids, nicotine have also investigated. Preclinical suggests that reduce related outcomes. main proposed reward processing, stress, cognitive function, well broader satiety, changes gastric motility, glucose homeostasis. More in-depth mechanistic studies warranted. Clinical their findings less conclusive; most support safety efficacy ASUD treatment. Identifying preferred compounds, subgroups who responsive some key questions translate promising data into clinical settings. Several trials underway test people ASUDs.
Language: Английский
Citations
13
Addiction Biology, Journal Year: 2024, Volume and Issue: 29(4)
Published: April 1, 2024
Abstract One of the leading drug addiction theories states that habits and underlying neural process a ventral to dorsal striatal shift are building blocks compulsive drug‐seeking behaviour compulsion is maladaptive persistence responding despite adverse consequences. Here we discuss as defined primarily from perspective animal experimentation falls short clinical phenomena their neurobiological correlates. Thus for human condition, concept should be critically addressed potentially revised.
Language: Английский
Citations
5
Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 50(2), P. 444 - 451
Published: Sept. 16, 2024
The cyclic adenosine monophosphate (cAMP) cascade is thought to play an important role in regulating alcohol-dependent behaviors, with potentially opposite effects following acute versus chronic administration. Phosphodiesterase 4 (PDE4) the primary brain enzyme that metabolizes cAMP, thereby terminating its signal. Radioligand binding PDE4 serves as indirect biomarker of cAMP activity, cAMP-protein kinase A (PKA)-mediated phosphorylation increases affinity for radioligand ~10-fold. Of four subtypes, PDE4B polymorphisms are known be strongly associated alcohol and substance use disorders. This study imaged rats PDE4B-preferring positron emission tomography (PET) [18F]PF-06445974 ethanol administration, aiming explore potential PET imaging future human studies. Compared control group treated saline, administration (i.p. 0.5 g/kg) significantly increased whole uptake early 30 minutes post-exposure. effect persisted at 2 hours, peaked diminished 6 hours 24 In contrast, a rat model dependence, was reduced 5 post-exposure normalized by 3 days. reduction may reflect long-term adaptation repeated alcohol-induced activation signaling exposure. Taken together, results suggest individuals disorder (AUD) should considered conjunction ongoing trials inhibitors treat withdrawal reduce consumption.
Language: Английский
Citations
4
Neurobiology of Stress, Journal Year: 2025, Volume and Issue: 35, P. 100713 - 100713
Published: Feb. 8, 2025
The Gut Microbiome-Liver-Brain Axis is a relatively novel construct with promising potential to enhance our understanding of Alcohol Use Disorder (AUD), and its therapeutic approaches. Significant alterations in the gut microbiome occur AUD even before any other systemic signs or symptoms manifest. Prolonged inappropriate alcohol consumption, by affecting microbiota mucosa permeability, thought contribute development behavioral cognitive impairments, leading Alcohol-Related Liver Disorders potentially progressing into alcoholic cirrhosis, which often associated severe impairment related neurodegeneration, such as hepatic encephalopathy dementia. critical role further supported efficacy FDA-approved treatments for cirrhosis (i.e., lactulose rifaximin). To stimulate new research, we hypothesize that interactions between maladaptive stress response constitutional predisposition neurodegeneration underlie progression conditions Clinical Concerns impairment, represent significant costly burden society. Early identification individuals at risk developing these could help prioritize integrated interventions targeting different substrates axis. Specifically, addiction medications, modulators, stress-reducing interventions, and, possibly soon, agents reduce steatosis/fibrosis will be discussed context digitally explicit goal this treatment performed on early stage disorder would transition from those Common strategy recommended most neurological neurodegenerative disorders.
Language: Английский
Citations
0
Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown, P. 111341 - 111341
Published: March 1, 2025
Language: Английский
Citations
0
Psychopharmacology, Journal Year: 2025, Volume and Issue: unknown
Published: March 31, 2025
Abstract Rationale Negative affect plays a prominent role in the maintenance of alcohol use disorder (AUD) and has been identified as risk factor for relapse to alcohol. To date, however, treatment options that target negative affective states consecutive AUD are insufficient. Oxytocin (OXY) might be promising approach addressing resulting motivation Objectives We aimed investigate acute effects 24 I.U. OXY, administered intranasally, compared matched placebo (PLC) on central processing emotional stimuli amygdala individuals with AUD. Methods conducted randomized double-blind placebo-controlled crossover study N = Amygdala response served primary outcome was assessed using validated functional magnetic resonance imaging emotion-processing task. Alcohol craving secondary outcome. Results OXY versus PLC attenuated right reactivity fearful angry face during fMRI task ( t (33) 3.32, p FWE =0.035), while no effect activation observed presentation geometric figures. In addition, positively associated r =.332, Bias corrected accelerated 95% confidence interval [95% BCa CI]=-0.044 0.624, =.042). Conclusions OXY’s neurocircuitry underlying support its potential dampening induced by implicate future option Clinicaltrials registry DRKS00026218.
Language: Английский
Citations
0
Brain Sciences, Journal Year: 2025, Volume and Issue: 15(6), P. 542 - 542
Published: May 22, 2025
Background: Alcohol Use Disorder (AUD) is highly prevalent among substance use disorders worldwide and characterized by a multifactorial pathophysiology. AUD treatment mostly based on combined pharmacotherapy multidisciplinary clinical approaches. Nonetheless, meta-analytical studies assessing the efficacy of combination therapy are scarcely available. Methods: We searched for randomized trials through PubMed, ClinicalTrials.gov, Cochrane Library, SciELO, Biblioteca Virtual em Saúde, Google Scholar databases. Original published in English Portuguese were selected. Data collection followed PRISMA MOOSE guidelines was assessed using Risk Bias Tool (RoB 2). Heterogeneity Q test. Meta-regression conducted Egger’s regression method. Twelve articles finally included analysis, random-effects models applied aggregate trial results. Results: The meta-analysis found that therapies led to an average 4.045% increase abstinence rates (95% CI: 0.415% 7.675%) compared monotherapies. showed strong positive association between naltrexone, acamprosate, sertraline—either alone or combination—and success AUD. meta-regression also highlighted impact patients’ variables, such as gender, age, country, psychiatric comorbidities, their outcomes. These findings may identify potential therapeutic pathway promoting alcohol abstinence, further supported Number Needed Treat (NNT) 25, acceptable value disorder treatments. Conclusions: Combined pharmacotherapies more effective than monotherapy enhancing treatment, with sertraline emerging key adjunctive agents these underscore complexity condition highlight promising strategy achieving better outcomes, particularly terms rates.
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1482 - 1482
Published: Jan. 25, 2024
Tobacco smoking is the leading cause of preventable death and disease. Although there are some FAD-approved medicines for controlling smoking, relapse rate remains very high. Among factors that could induce nicotine relapse, stress might be most important one. In last decades, preclinical studies have generated many new findings lead to a better understanding stress-induced nicotine-seeking. Several molecules such as α3β4 nicotinic acetylcholine receptor, α2-adrenergic receptors, cannabinoid receptor 1, trace amine-associated neuropeptide systems (corticotropin-releasing factor its dynorphine kappa opioid receptor) been linked relapse. this review, we discuss recent advances in neurobiology, treatment targets, potential therapeutics We also may influence should considered future studies. final section, perspective on research directions provided. Further investigation neurobiology will shed light development help us understand interactions between reward brain.
Language: Английский
Citations
3
Pharmacological Research, Journal Year: 2024, Volume and Issue: 209, P. 107462 - 107462
Published: Oct. 11, 2024
Epidemiological data indicate a strong association between alcohol use disorder (AUD) and neuropathic pain. Genetically-selected Marchigian Sardinian alcohol-preferring (msP) rats exhibit high preference for compared with their background strain (Wistar rats), but sensitivity to mechanical allodynia after chronic exposure is unknown. The present study the development of "low, non-pathological drinker" Wistar "high msP using two-bottle choice (2BC) free-access procedure. Several studies reported involvement endocannabinoids (eCBs) in modulating allodynia, there are no on role alcohol-related allodynia. Thus, assessed eCBs related lipid species lumbar dorsal root ganglia (DRG) correlated them our model. We found that male female developed persistent during protracted abstinence from alcohol, presenting sign recovery, as opposed rats. This effect directly total intake. Notably, we correlation lower DRG 2-arachidonoylglycerol (2-AG) levels higher both sexes not Moreover, alcohol-exposed abstinent females males exhibited significant alterations thromboxane B2 prostaglandin E2/prostaglandin D2 naive These findings demonstrate 2-AG metabolism altered prolonged represents potentially interesting pharmacological target treatment abstinence.
Language: Английский
Citations
3
PsyCh Journal, Journal Year: 2024, Volume and Issue: unknown
Published: July 5, 2024
Abstract Reward processing dysfunction and inhibition control deficiency have been observed in Internet gaming disorder (IGD). However, it is still unclear whether the previous reinforcement learning depends on reward/punishment feedback influences cognitive inhibitory of IGD. This study compared differences between an IGD group healthy people without game experiences probability selection task subsequent stop signal by method behavioral experiments, order to explore reward ability impaired group. We also discuss influence control. The results showed that (1) during phase, group's accuracy was significantly lower than group; (2) with group, reaction times were longer transfer phase; (3) for no‐go trials phase after learning, reward‐related stimulation punishment‐related or neutral stimulation, but there no significant difference among three conditions These findings indicated impaired, which further caused abnormal response stimuli.
Language: Английский
Citations
2