Innovative therapeutic strategies using ADHD medications tailored to the behavioral characteristics of patients with chronic pain

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 26, 2025

Chronic pain affects a significant portion of adults and is linked to psychosocial issues, cognitive dysfunction, psychiatric disorders, complicating treatment. Attention deficit hyperactivity disorder (ADHD) increasingly recognized as contributing factor chronic pain, particularly nociplastic with notable prevalence comorbidity between ADHD conditions like fibromyalgia low back pain. behaviors such impulsivity overactivity can exacerbate by leading patients seek risky treatments or discontinue care prematurely. medications are expected alleviate severity improving associated dysfunction addressing central sensitization, fundamental mechanism in Brain abnormalities contribute increased spontaneous activity the anterior cingulate cortex-posterior insular pathway due neuroinflammation, alterations action potential firing, changes transmission pathways spinal dorsal horn. Additionally, norepinephrine synthesis reduced efficiency amplify nociceptive information from periphery facilitate sensitization ADHD. Beyond typical stimulants, reuptake inhibitors, alpha-2 receptor agonists, various antidepressants, mood stabilizers, antipsychotics, Parkinson's disease medications, antidementia have proven effective alleviating symptoms. These for ADHD, may offer innovative solutions managing targeting both cognitive/behavioral observed comorbid Further research into these mechanisms could lead new, more pharmacological condition that often overlooked.

Language: Английский

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Central Med23 deficiency leads to malformation of dentate gyrus and ADHD-like behaviors in mice

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

Published: March 20, 2025

Abstract Attention-deficit hyperactivity disorder (ADHD) is a prevalent psychiatric with high heritability, while its etiology and pathophysiology remain unclear. Med23 subunit of the Mediator complex, key regulator gene expression by linking transcription factors to RNA polymerase II. The mutations are associated several brain diseases including microcephaly, epilepsy intellectual disability, but biological roles in development possible behavioral consequence have not been explored animal model. In this study, Emx1-Cre mice were used generate conditional knockout (Med23 CKO) that showed severe hypoplasia dentate gyrus (DG) malformation dendritic tree spines along impaired short-term synaptic plasticity. Interestingly, CKO exhibited ADHD-like behaviors as shown hyperactivity, inattention impulsivity, well sensory gating working memory. Importantly, methylphenidate (MPH), common drug for ADHD ameliorated these deficits mice. Furthermore, we also revealed plasticity was partially restored MPH an N-methyl-d-aspartate (NMDA) receptor-dependent way. Collectively, our data demonstrate deficiency causes DG behaviors, suggesting novel mechanism underlying relevant diseases.

Language: Английский

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Rodent models of attention-deficit hyperactivity disorder: An updated framework for model validation and therapeutic drug discovery

Pharmacology Biochemistry and Behavior, Journal Year: 2022, Volume and Issue: 216, P. 173378 - 173378

Published: March 31, 2022

Language: Английский

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Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits

Advances in Drug and Alcohol Research, Journal Year: 2023, Volume and Issue: 3

Published: Aug. 11, 2023

Maternal tobacco use and nicotine exposure during pregnancy have been associated with adverse birth outcomes in infants can lead to preventable complications. Exposure other compounds electronic cigarettes (e-cigarettes) has shown increases the risk of miscarriage, prematurity, stillbirth, low weight, perinatal morbidity, sudden infant death syndrome (SIDS). Additionally, recent data provided by clinical pre-clinical research demonstrates that may heighten for neurodevelopmental disorders such as Attention-Deficit Hyperactivity (ADHD), anxiety, depression along altering underlying brain circuitry, response neurotransmitters, volume. In United States, one 14 women (7.2%) reported smoked their global prevalence smoking estimated be 1.7%. Approximately 1.1% States also used e-cigarettes last 3 months pregnancy. Due large percentage utilizing products globally, this review seeks centralize studies focused on neurobehavioral complications prenatal (PNE) alterations hypothalamic-pituitary-adrenal (HPA) axis regions prefrontal cortex (PFC), ventral tegmental area (VTA), nucleus accumbens (NA), hippocampus, caudate well changes nAChR cholinergic receptor signaling, long-term drug seeking behavior following PNE, related developmental disorders. Current literature analyzing association between PNE offspring developing schizophrenia, attention-deficit hyperactivity disorder autism spectrum (ASD), obesity will discussed.

Language: Английский

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Reveal the main factors and adsorption behavior influencing the adsorption of pollutants on natural mineral adsorbents: Based on machine learning modeling and DFT calculation

Separation and Purification Technology, Journal Year: 2023, Volume and Issue: 331, P. 125706 - 125706

Published: Nov. 15, 2023

Language: Английский

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Regrettable Substitutes and the Brain: What Animal Models and Human Studies Tell Us about the Neurodevelopmental Effects of Bisphenol, Per- and Polyfluoroalkyl Substances, and Phthalate Replacements

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 6887 - 6887

Published: June 23, 2024

In recent decades, emerging evidence has identified endocrine and neurologic health concerns related to exposure endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA), certain per- polyfluoroalkyl compounds (PFASs), phthalates. This resulted in consumer pressure remove these from the market, especially food-contact materials personal care products, driving their replacement with structurally or functionally similar substitutes. However, "new-generation" may be just as more harmful than predecessors some have not received adequate testing. review discusses research on early-life exposures new-generation bisphenols, PFASs, phthalates links neurodevelopmental behavioral alterations zebrafish, rodents, humans. As a whole, suggests that BPA alternatives, BPAF, newer such GenX, can significant effects neurodevelopment. The need for further research, regarding phthalate replacements bio-based is briefly discussed.

Language: Английский

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Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 30, 2022

The functional and pharmacological significance of the dopamine D4 receptor (D4R) has remained least well understood all subtypes. Even more enigmatic been role very prevalent human DRD4 gene polymorphisms in region that encodes third intracellular loop receptor. most common encode a D4R with 4 or 7 repeats proline-rich sequence 16 amino acids (D4.4R D4.7R). have associated individual differences linked to impulse control-related neuropsychiatric disorders, consistent associations established between encoding D4.7R attention-deficit hyperactivity disorder (ADHD) substance use disorders. function its polymorphic variants is being revealed by addressing heteromerization relatively avidity norepinephrine for D4R. We review evidence conveying significant differential D4.4R dopaminergic noradrenergic modulation frontal cortico-striatal pyramidal neuron, implications moderation constructs impulsivity as personality traits. This depends on their ability confer different properties adrenergic α2A (α2AR)-D4R heteromers D2 (D2R)-D4R heteromers, preferentially localized perisomatic cortical neuron striatal terminals, respectively. also support therapeutic target ADHD other impulse-control restless legs syndrome.

Language: Английский

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Dexmedetomidine alleviates host ADHD-like behaviors by reshaping the gut microbiota and reducing gut-brain inflammation

Psychiatry Research, Journal Year: 2023, Volume and Issue: 323, P. 115172 - 115172

Published: March 20, 2023

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders that affects children and even continues into adulthood. Dexmedetomidine (DEX), a short-term sedative, can selectively activate α2-adrenoceptor. Treatment with α2-adrenergic agonists in patients ADHD becoming increasingly common. However, therapeutic potential DEX for treatment unknown. Here, we evaluated effect on ADHD-like behavior spontaneously hypertensive rats (SHRs), widely used animal model ADHD. ameliorated hyperactivity spatial working memory deficits normalized θ electroencephalogram (EEG) rhythms SHRs. We also found altered gut microbiota composition promoted enrichment beneficial bacterial genera associated anti-inflammatory effects The pathological scores permeability level inflammation observed brain were remarkably improved after administration. Moreover, transplantation fecal from DEX-treated SHRs produced mimicked Therefore, promising functions by reshaping reducing brain.

Language: Английский

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Animal Models of Childhood Exposure to Lead or Manganese: Evidence for Impaired Attention, Impulse Control, and Affect Regulation and Assessment of Potential Therapies

Neurotherapeutics, Journal Year: 2023, Volume and Issue: 20(1), P. 3 - 21

Published: Jan. 1, 2023

Behavioral disorders involving attention and impulse control dysfunction, such as ADHD, are among the most prevalent in children adolescents, with significant impact on their lives. The etiology of these is not well understood, but recognized to be multifactorial, studies reporting associations polygenic environmental risk factors, including toxicant exposure. Environmental epidemiological studies, while good at establishing a variety genetic cannot establish causality. Animal models behavioral disorders, when properly designed, can play an essential role causal relationships between factors disorder, provide model systems for elucidating underlying neural mechanisms testing therapies. Here, we review how animal developmental lead or manganese exposure have been pivotal (1) relationship lasting dysfunction domains attention, control, affect regulation, (2) efficacy specific therapeutic approaches alleviating deficits. case illustrate advance knowledge ways that possible human studies. For example, contrast Treatment Lead Poisoned Children (TLC) clinical trial evaluating succimer chelation improve cognitive functioning lead-exposed children, our showed produce benefits if sufficiently reduces brain levels. In addition, this study revealed treatment absence produces highlighting potential risks off-label uses, autistic without history Our has demonstrated cause attentional sensorimotor deficits, akin ADHD-inattentive phenotype, thereby providing insights into exposures contributors ADHD. These also shown oral methylphenidate (Ritalin) fully alleviate deficits produced by early Mn Future work should continue focus development use appropriately recapitulate complex phenotypes order determine mechanistic basis caused toxicants, existing emerging

Language: Английский

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Theobromine improves hyperactivity, inattention, and working memory via modulation of dopaminergic neural function in the frontal cortex of spontaneously hypertensive rats

Food & Function, Journal Year: 2024, Volume and Issue: 15(10), P. 5579 - 5595

Published: Jan. 1, 2024

Attention-deficit/hyperactivity disorder (ADHD) is a developmental and dopaminergic dysfunction in the prefrontal cortex (PFC) may play role. Our previous research indicated that theobromine (TB), methylxanthine, enhances cognitive function rodents via PFC. This study investigates TB's effects on hyperactivity stroke-prone spontaneously hypertensive rats (SHR), an ADHD animal model. Male SHRs (6-week old) received diet containing 0.05% TB for 40 days, while control normal diets. Age-matched male Wistar-Kyoto (WKY) served as genetic controls. During administration period, we conducted open-field tests Y-maze tasks to evaluate function, then assessed dopamine concentrations tyrosine hydroxylase (TH), receptor D1-5 (DRD1-5), transporter (DAT), vesicular monoamine transporter-2 (VMAT-2), synaptosome-associated protein-25 (SNAP-25), brain-derived neurotrophic factor (BDNF) expressions Additionally, binding affinity of adenosine receptors (ARs) was evaluated. Compared WKY, SHR exhibited hyperactivity, inattention working memory deficits. However, chronic significantly improved these ADHD-like behaviors SHR. also normalized expression levels TH, DRD2, DRD4, SNAP-25, BDNF PFC No changes were observed DRD1, DRD3, DRD5, DAT, VMAT-2 between WKY rats, intake had minimal effects. found have ARs. These results indicate long-term supplementation mitigates deficits by modulating nervous PFC, representing potential adjunctive treatment ADHD.

Language: Английский

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