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Pharmacology, Biochemistry, and Behavior Sep 2023Substance dependence is a disorder that alters the functioning of the nervous system due to frequent abuse of drugs. The role of dopamine in the addictive effect of...
Substance dependence is a disorder that alters the functioning of the nervous system due to frequent abuse of drugs. The role of dopamine in the addictive effect of psychostimulants is well known; however, the involvement of the noradrenergic system is still unclear and poorly understood, though drugs like cocaine and amphetamines are known to exert significant activity on this system. The drug modafinil (MOD) has no proven addictive effect. It promotes wakefulness by acting mainly on the dopaminergic system and, to a lesser degree, the noradrenergic (NOR) system. Atomoxetine (ATX) is a non-stimulant drug that acts only on the NOR system, enhancing its activity. The aims of the present study were to analyze the effect of co-activating the DA and NOR systems (with MOD and ATX, respectively) on motor activity and exploratory behavior, and to examine the possible emergence of rewarding properties of MOD and an MOD+ATX mixture. Male Wistar rats at postnatal day 60 were treated chronically (16 days) with either monotherapy with 2ATX, 4ATX, or 60MOD mg/kg, two combinations of these substances -60MOD + 2ATX and 60MOD + 4ATX- or a vehicle. The rats co-administered with 60MOD + 4ATX reduced the rearing behavior frequency induced by MOD, but this behavior was sensitized by self-administration of the MOD+ATX mixture after chronic treatment. The rats pre-treated with 60MOD + 4ATX showed higher self-administration of MOD and greater activity on an operant task to obtain the MOD+ATX mixture. In addition, the 60MOD, 2ATX, and 60MOD + 2ATX groups showed sensitization of exploratory behavior after ingesting the mixture. Results suggest that the noradrenergic system enhances the incentive value of MOD and a MOD+ATX mixture, while also playing an important role in the sensitization of exploratory behavior.
Topics: Male; Animals; Rats; Rats, Wistar; Exploratory Behavior; Motivation; Modafinil; Atomoxetine Hydrochloride; Dopamine
PubMed: 37595803
DOI: 10.1016/j.pbb.2023.173618 -
ACS Pharmacology & Translational Science Oct 2023Chronic stressful situations result in altered monoaminergic activity of neurotransmitters, resulting in various conditions characterized by deficits in learning, memory...
PURPOSE
Chronic stressful situations result in altered monoaminergic activity of neurotransmitters, resulting in various conditions characterized by deficits in learning, memory and attention. Stimulant effects can be visualized in terms of increased cognitive abilities through enhancement of dopamine (DA) release.
METHOD
This study examined cognitive responses and brain DA and 5-hydroxytryptamine (5HT) levels after prolonged methylphenidate (MPH) and modafinil administration, to demonstrate their effect on stress-induced cognitive deficits in rats. Effects on cognition were evaluated by passive avoidance and water maze tests. Furthermore brain levels of DA, homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 5HT and 5-hydroxyindoleacetic acid (5HIAA) were analyzed by high-performance liquid chromatography coupled with electrochemical detection.
RESULTS
We found that both MPH and modafinil improved cognition in both restrained and unrestrained rats, as examined through water maze and passive avoidance tests. Furthermore, these substance were associated with increased brain DA and 5-HT levels. Notabily, we observed decrease in DOPAC and HVA levels, while 5-HIAA levels exhibited a slight increase.
CONCLUSIONS
The prevention of stress-induced cognitive deficits by MPH and modafinil could be elucidated through the interaction between 5HT and DA in regulating cognitive function.
PubMed: 37854618
DOI: 10.1021/acsptsci.3c00077 -
Journal of Neurosurgical Sciences Aug 2023Modafinil has been proven to exert anti-inflammatory, anti-oxidative and neuroprotective effects on numerous neurological disorders. However, its effects after traumatic...
BACKGROUND
Modafinil has been proven to exert anti-inflammatory, anti-oxidative and neuroprotective effects on numerous neurological disorders. However, its effects after traumatic brain injury (TBI) have not been yet explored. The aim of this study was to explore if Modafinil can attenuate the neuroinflammatory phase of TBI and clarify the possible underlying mechanisms.
METHODS
A weight drop model was used to induce experimental TBI on 30 Wistar albino rats. The treatment group received Modafinil on the day of the trauma and the following 5 days. Garcia Test was used to assess for neurological status and histopathological examination along with biochemical analysis of NSE, S-100B, CASP3, and TBARS levels were performed.
RESULTS
Rats treated with Modafinil after the trauma had a statistically significant higher Garcia Test Score (P<0.001) and presented with increased evidence of anti-inflammatory and neuroprotective effect (P<0.05, P=0.005). Decreased levels of all biochemical parameters with NSE, CASP3, and TBARS having statistical significance was observed (P<0.05).
CONCLUSIONS
The findings of this paper support the notion that a psychoactive drug Modafinil, traditionally used for sleep disorders and also known as a cognitive enhancer may prove beneficial in decreasing mortality and morbidity after TBI through anti-inflammatory, anti-oxidative and neuroprotective effects.
Topics: Rats; Animals; Modafinil; Caspase 3; Neuroprotective Agents; Thiobarbituric Acid Reactive Substances; Rats, Wistar; Brain Injuries, Traumatic; Inflammation; Anti-Inflammatory Agents; Disease Models, Animal
PubMed: 34545730
DOI: 10.23736/S0390-5616.21.05382-0 -
Purinergic Signalling Nov 2023Adenosine receptor (AR) suppresses inflammation and fibrosis by activating cyclic adenosine monophosphate (cAMP) signaling. We investigated whether altered AR expression...
Adenosine receptor (AR) suppresses inflammation and fibrosis by activating cyclic adenosine monophosphate (cAMP) signaling. We investigated whether altered AR expression contributes to the development of fibrotic diseases and whether AAR and AAR upregulation inhibits fibrotic responses. Primary human lung fibroblasts (HLFs) from normal (NHLFs) or patients with idiopathic pulmonary fibrosis (DHLF) were used for in vitro testing. Murine models of fibrotic liver or pulmonary disease were developed by injecting thioacetamide intraperitoneally, by feeding a high-fat diet, or by intratracheal instillation of bleomycin. Modafinil, which activates cAMP signaling via AAR and AAR, was administered orally. The protein amounts of AAR, AAR, and exchange protein directly activated by cAMP (Epac) were reduced, while collagen and α-smooth muscle actin (α-SMA) were elevated in DHLFs compared to NHLFs. In liver or lung tissue from murine models of fibrotic diseases, AAR and AAR were downregulated, but AAR and AAR were not. Epac amounts decreased, and amounts of collagen, α-SMA, K2.3, and K3.1 increased compared to the control. Modafinil restored the amounts of AAR, AAR, and Epac, and reduced collagen, α-SMA, K2.3, and K3.1 in murine models of fibrotic diseases. Transforming growth factor-β reduced the amounts of AAR, AAR, and Epac, and elevated collagen, α-SMA, K2.3, and K3.1 in NHLFs; however, these alterations were inhibited by modafinil. Our investigation revealed that AAR and AAR downregulation induced liver and lung fibrotic diseases while upregulation attenuated fibrotic responses, suggesting that AAR and AAR-upregulating agents, such as modafinil, may serve as novel therapies for fibrotic diseases.
PubMed: 37938538
DOI: 10.1007/s11302-023-09973-8 -
Clinical Gastroenterology and... Jan 2024Fatigue is highly prevalent in patients with IBD, affecting 72% of patients with active inflammatory bowel disease (IBD) and 47% in remission, and is associated with...
Fatigue is highly prevalent in patients with IBD, affecting 72% of patients with active inflammatory bowel disease (IBD) and 47% in remission, and is associated with poor quality of life and significantly wider costs. However, understanding the mechanisms of IBD fatigue remains limited, as reflected in a lack of effective treatments..
PubMed: 38191015
DOI: 10.1016/j.cgh.2023.12.030 -
Acta Psychiatrica Scandinavica Dec 2023In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired...
Effects of maternal modafinil treatment on fetal development and neonatal growth parameters - a multicenter case series of the European Network of Teratology Information Services (ENTIS).
OBJECTIVE
In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired fetal growth were reported, although study results were conflicting. Our investigation aims to examine previously reported safety signals.
METHOD
Multicenter case series based on data from 18 Teratology Information Services from 12 countries. Modafinil exposed pregnancies with an estimated date of birth before August 2019 were included in this study. For prospectively ascertained pregnancies, cumulative incidences of pregnancy outcomes, rate of nonchromosomal MCA in first trimester exposed pregnancies and percentiles of neonatal/infant weight and head circumference (HC) were calculated. Potential dose-dependent effects on fetal growth were explored by linear regression models. Retrospectively ascertained cases were screened for pattern of MCA and other adverse events.
RESULTS
One hundred and seventy-five prospectively ascertained cases were included, of which 173 were exposed at least during the first trimester. Cumulative incidences for live birth, spontaneous abortion and elective termination of pregnancy were 76.9% (95% CI, 68.0%-84.8%), 9.3% (95% CI, 5.0%-16.9%), and 13.9% (95% CI, 8.1%-23.1%), respectively. Nonchromosomal MCA was present in 3/150 live births, corresponding to an MCA rate of 2.0% (95%CI, 0.6%-6.1%), none were reported in pregnancy losses. Compared to reference standards, birth weight (BW) tended to be lower and neonatal HC to be smaller in exposed newborns (data available for 144 and 73 of 153 live births, respectively). In nonadjusted linear regression models, each 100 mg increase of average dosage per pregnancy day was associated with a decrease in standard deviation score (SDS) of -0.28 SDS (95% CI, -0.45 to -0.10) for BW and of -0.28 SDS (95% CI, -0.56 to 0.01) for HC. Screening of 22 retrospectively reported cases did not reveal any specific pattern of MCA or other adverse outcomes.
CONCLUSION
The results do not indicate an increased risk of MCA after in utero exposure to modafinil, but a tendency toward lower BW and reduced neonatal HC. However, these findings should be regarded as preliminary. Until further studies allow for a definite conclusion, modafinil should not be used during pregnancy.
PubMed: 38110225
DOI: 10.1111/acps.13643 -
Brain and Behavior Feb 2024There is media concern over students using prescription stimulants as "cognitive enhancers" to try and improve their academic performance. However, there is limited... (Review)
Review
INTRODUCTION
There is media concern over students using prescription stimulants as "cognitive enhancers" to try and improve their academic performance. However, there is limited evidence about the prevalence of this behaviour in the United Kingdom, or whether it has increased in recent years.
METHODS
We review survey studies on students' use of cognitive enhancers.
RESULTS
Overall reported use is low, with some inconclusive evidence that it is increasing. Use of modafinil appears to be higher than that of methylphenidate or dexamphetamine.
CONCLUSION
There is a clear need for large-scale research in this area, using representative sampling and survey methods that protect student anonymity.
Topics: Humans; Prevalence; Universities; Central Nervous System Stimulants; Students; Nootropic Agents; Prescriptions
PubMed: 38346719
DOI: 10.1002/brb3.3419 -
BMJ Supportive & Palliative Care Sep 2023Cancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Cancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no consensus on pharmacologic interventions for treating CRF. The aim of this systematic review is to provide more clarity on which pharmacologic interventions may be most promising, for future clinical trials. The network meta-analysis provides the ability to compare multiple agents when no direct head-to-head trials of all agents have been performed.
METHODS
Medline (PubMed), EMBASE and Cochrane Central Register of Controlled Trials were searched up until 5 March 2021. Studies were included if they reported on a pharmacologic intervention for CRF. Standardised mean differences and corresponding 95% CIs were computed using a random-effects maximum-likelihood model.
RESULTS
This review reports on 18 studies and 2604 patients, the most comprehensive review of pharmacologic interventions for CRF at the time of this publication. Methylphenidate, modafinil and paroxetine were superior to placebo. Methylphenidate and modafinil were equivalent to one another. Paroxetine was superior to modafinil.
CONCLUSION
Paroxetine should be further studied in future trials. As well, more safety data are needed on pharmacologic interventions.
Topics: Humans; Modafinil; Central Nervous System Stimulants; Paroxetine; Network Meta-Analysis; Methylphenidate; Fatigue; Neoplasms
PubMed: 34593386
DOI: 10.1136/bmjspcare-2021-003244 -
Pediatric Research Apr 2024The aim of this scoping review is to examine the extent and depth of the literature on effects of central nervous system (CNS) stimulant medications on physical function... (Review)
Review
The aim of this scoping review is to examine the extent and depth of the literature on effects of central nervous system (CNS) stimulant medications on physical function in children with cerebral palsy (CP). A systematic search for relevant peer-reviewed studies was conducted of PubMed, CINAHL, Cochrane, SPORTDiscus, Embase, & Scopus (January 2002 & August 2022). We included studies that examined the effects of CNS stimulants on physical function in children with CP. Four studies met our selection criteria. All studies explored the effect of Modafinil on physical function outcomes. Three studies of the four included studies reported positive effects of Modafinil on spasticity, motor performance, and gait, whereas one study reported no significant effects of Modafinil. Our findings suggest that there is very low-quality evidence that suggests that Modafinil may enhance physical improvements in body structure and function, including reduction in spasticity and improvements in gait parameters. IMPACT: Central nervous system stimulants were examined for efficacy on physical function and spasticity in children with cerebral palsy. The evidence on the effects of central nervous system stimulants on physical function in children with CP is limited and inconsistent.
Topics: Child; Humans; Central Nervous System Stimulants; Cerebral Palsy; Gait; Modafinil; Muscle Spasticity; Treatment Outcome
PubMed: 38071277
DOI: 10.1038/s41390-023-02933-3 -
International Journal of Mental Health... Oct 2023The global rise in methamphetamine use and its negative effects warrants the need for research exploring harm reduction and treatment interventions for individuals with... (Review)
Review
Prescription psychostimulants as a harm reduction and treatment intervention for methamphetamine use disorder and the implications for nursing clinical practice: A scoping review of the literature.
The global rise in methamphetamine use and its negative effects warrants the need for research exploring harm reduction and treatment interventions for individuals with methamphetamine use disorder. Agonist medications have been utilized for years for the treatment of heroin and opioid addiction, but have yet to be incorporated into mainstream Canadian practice for methamphetamine dependence. This review aims to provide an overview of the current trends of prescription psychostimulant usage for individuals with methamphetamine use disorder from a Canadian perspective, identifies the barriers to accessing prescription psychostimulants for methamphetamine use disorder and highlights the nursing clinical practice implications in caring for individuals with the disorder. Discourse on the sustained abstinence and harm reduction debate is presented from the perspective of methamphetamine abuse is provided along with the neuropsychiatric complications of chronic methamphetamine use. The impacts of specific prescription psychostimulants on cognition are discussed as is the use of neuroimaging techniques to assess neuronal damage in methamphetamine users. Sign of toxicity, overdose and the contraindications for use of these prescription psychostimulants is also presented. The implications to nursing clinical practice in caring for this population is provided, touching on the clinical presentation of methamphetamine use, completing thorough assessment and screening and patient education. The findings of this review indicate the need for further research in this area exploring the benefits of prescription psychostimulants as a harm reduction and treatment intervention for the global problem of methamphetamine dependence.
Topics: Humans; Methamphetamine; Harm Reduction; Canada; Central Nervous System Stimulants; Amphetamine-Related Disorders; Prescriptions
PubMed: 36978242
DOI: 10.1111/inm.13144