Role of Adenosine in the Pathophysiology and Treatment of Attention Deficit Hyperactivity Disorder

Overview

Journal Purinergic Signal

Publisher Springer

Date 2024 Oct 31

PMID 39480600

Authors

Qingxia Jia

Hongwan Tan

Tingsong Li

Xiaoling Duan

Affiliations

Soon will be listed here.

Abstract

Attention deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental condition characterized by persistent inattention, hyperactivity, and impulsivity. Although its precise etiology remains unclear, current evidence suggests that dysregulation within the neurotransmitter system plays a key role in the pathogenesis of ADHD. Adenosine, an endogenous nucleoside widely distributed throughout the body, modulates various physiological processes, including neurotransmitter release, sleep regulation, and cognitive functions through its receptors. This review critically examines the role of the adenosine system in ADHD, focusing on the links between adenosine receptor function and ADHD-related symptoms. Additionally, it explores how adenosine interacts with dopamine and other neurotransmitter pathways, shedding light on its involvement in ADHD pathophysiology. This review aims to provide insights into the potential therapeutic implications of targeting the adenosine system for ADHD management.

References

Polanczyk G, Silva de Lima M, Horta B, Biederman J, Rohde L . The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007; 164(6):942-8. DOI: 10.1176/ajp.2007.164.6.942. View

Gerfen C, Surmeier D . Modulation of striatal projection systems by dopamine. Annu Rev Neurosci. 2011; 34:441-66. PMC: 3487690. DOI: 10.1146/annurev-neuro-061010-113641. View

Paine T, Neve R, Carlezon Jr W . Attention deficits and hyperactivity following inhibition of cAMP-dependent protein kinase within the medial prefrontal cortex of rats. Neuropsychopharmacology. 2009; 34(9):2143-55. PMC: 2721023. DOI: 10.1038/npp.2009.40. View

Howe M, Dombeck D . Rapid signalling in distinct dopaminergic axons during locomotion and reward. Nature. 2016; 535(7613):505-10. PMC: 4970879. DOI: 10.1038/nature18942. View

Molero Y, Gumpert C, Serlachius E, Lichtenstein P, Walum H, Johansson D . A study of the possible association between adenosine A2A receptor gene polymorphisms and attention-deficit hyperactivity disorder traits. Genes Brain Behav. 2013; 12(3):305-10. DOI: 10.1111/gbb.12015. View

Kim M, Kim H, Jin H . Genetic association between ADRB2 rs1042713 and elite athletic performances in the Korean population. Gene. 2023; 896:148037. DOI: 10.1016/j.gene.2023.148037. View

Huang Z, Zhang Z, Qu W . Roles of adenosine and its receptors in sleep-wake regulation. Int Rev Neurobiol. 2014; 119:349-71. DOI: 10.1016/B978-0-12-801022-8.00014-3. View

Chen J, Zhao Y, Luo X, Hong H, Yang T, Huang S . NLR surveillance of pathogen interference with hormone receptors induces immunity. Nature. 2022; 613(7942):145-152. DOI: 10.1038/s41586-022-05529-9. View

Conde S, Gonzalez C, Batuca J, Monteiro E, Obeso A . An antagonistic interaction between A2B adenosine and D2 dopamine receptors modulates the function of rat carotid body chemoreceptor cells. J Neurochem. 2008; 107(5):1369-81. DOI: 10.1111/j.1471-4159.2008.05704.x. View

10.

Pinho D, Quintas C, Sardo F, Cardoso T, Queiroz G . Purinergic modulation of norepinephrine release and uptake in rat brain cortex: contribution of glial cells. J Neurophysiol. 2013; 110(11):2580-91. DOI: 10.1152/jn.00708.2012. View

11.

Allgaier C, Hertting G, Huang H, Jackisch R . Protein kinase C activation and alpha 2-autoreceptor-modulated release of noradrenaline. Br J Pharmacol. 1987; 92(1):161-72. PMC: 1853609. DOI: 10.1111/j.1476-5381.1987.tb11308.x. View

12.

Quintas C, Goncalves J, Queiroz G . Involvement of P2Y, P2Y, A and A Receptors in the Purinergic Inhibition of NMDA-Evoked Noradrenaline Release in the Rat Brain Cortex. Cells. 2023; 12(13). PMC: 10341078. DOI: 10.3390/cells12131690. View

13.

Liu X, Ma L, Liu H, Gan J, Xu Y, Zhang T . Cell-Type-Specific Gene Inactivation and Restoration via Recombinase-Based Flipping of Targeted Genomic Region. J Neurosci. 2020; 40(37):7169-7186. PMC: 7480235. DOI: 10.1523/JNEUROSCI.1044-20.2020. View

14.

Marzocchi G, Oosterlaan J, Zuddas A, Cavolina P, Geurts H, Redigolo D . Contrasting deficits on executive functions between ADHD and reading disabled children. J Child Psychol Psychiatry. 2008; 49(5):543-52. DOI: 10.1111/j.1469-7610.2007.01859.x. View

15.

Yamahashi Y, Lin Y, Mouri A, Iwanaga S, Kawashima K, Tokumoto Y . Phosphoproteomic of the acetylcholine pathway enables discovery of the PKC-β-PIX-Rac1-PAK cascade as a stimulatory signal for aversive learning. Mol Psychiatry. 2022; 27(8):3479-3492. PMC: 9708603. DOI: 10.1038/s41380-022-01643-2. View

16.

Brown S, James S, Reddington M, Richardson P . Both A1 and A2a purine receptors regulate striatal acetylcholine release. J Neurochem. 1990; 55(1):31-8. DOI: 10.1111/j.1471-4159.1990.tb08817.x. View

17.

Guo S, Song Z, He J, Yin G, Zhu J, Liu H . Akt/Aquaporin-4 Signaling Aggravates Neuropathic Pain by Activating Astrocytes after Spinal Nerve Ligation in Rats. Neuroscience. 2021; 482:116-131. DOI: 10.1016/j.neuroscience.2021.12.015. View

18.

Van Dort C, Baghdoyan H, Lydic R . Adenosine A(1) and A(2A) receptors in mouse prefrontal cortex modulate acetylcholine release and behavioral arousal. J Neurosci. 2009; 29(3):871-81. PMC: 3430130. DOI: 10.1523/JNEUROSCI.4111-08.2009. View

19.

Jin S, Fredholm B . Adenosine A2A receptor stimulation increases release of acetylcholine from rat hippocampus but not striatum, and does not affect catecholamine release. Naunyn Schmiedebergs Arch Pharmacol. 1997; 355(1):48-56. DOI: 10.1007/pl00004917. View

20.

ORegan M, Simpson R, Perkins L, Phillis J . Adenosine receptor agonists inhibit the release of gamma-aminobutyric acid (GABA) from the ischemic rat cerebral cortex. Brain Res. 1992; 582(1):22-6. DOI: 10.1016/0006-8993(92)90312-w. View