Review of Rodent Models of Attention Deficit Hyperactivity Disorder

Overview

Journal Neurosci Biobehav Rev

Specialties Neurology
Psychology
Social Sciences

Date 2021 Dec 1

PMID 34848247

Citations 27

Authors

Samantha L Regan

Michael T Williams

Charles V Vorhees

Affiliations

Soon will be listed here.

Abstract

Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder that affects 8-12 % of children and >4 % of adults. Environmental factors are believed to interact with genetic predispositions to increase susceptibility to ADHD. No existing rodent model captures all aspects of ADHD, but several show promise. The main genetic models are the spontaneous hypertensive rat, dopamine transporter knock-out (KO) mice, dopamine receptor subtype KO mice, Snap-25 KO mice, guanylyl cyclase-c KO mice, and latrophilin-3 KO mice and rats. Environmental factors thought to contribute to ADHD include ethanol, nicotine, PCBs, lead (Pb), ionizing irradiation, 6-hydroxydopamine, neonatal hypoxia, some pesticides, and organic pollutants. Model validation criteria are outlined, and current genetic models evaluated against these criteria. Future research should explore induced multiple gene KOs given that ADHD is polygenic and epigenetic contributions. Furthermore, genetic models should be combined with environmental agents to test for interactions.

Citing Articles

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

Kasahara S, Takahashi M, Suto T, Morita T, Obata H, Niwa S Front Pharmacol. 2025; 16:1500313.

PMID: 40078279 PMC: 11896983. DOI: 10.3389/fphar.2025.1500313.

The impact of long-term isolation on anxiety, depressive-like and social behavior in aging Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) male rats.

Mamedova D, Nedogreeva O, Manolova A, Ovchinnikova V, Kostryukov P, Lazareva N Sci Rep. 2024; 14(1):28135.

PMID: 39548293 PMC: 11568175. DOI: 10.1038/s41598-024-79677-5.

Investigating the Impact of Nutrition and Oxidative Stress on Attention Deficit Hyperactivity Disorder.

Visternicu M, Rarinca V, Burlui V, Halitchi G, Ciobica A, Singeap A Nutrients. 2024; 16(18).

PMID: 39339712 PMC: 11435085. DOI: 10.3390/nu16183113.

Latrophilin-3 as a downstream effector of the androgen receptor induces bladder cancer progression.

Goto T, Teramoto Y, Nagata Y, Miyamoto H Discov Oncol. 2024; 15(1):440.

PMID: 39269616 PMC: 11399515. DOI: 10.1007/s12672-024-01324-2.

Effect of ginseng and ginsenosides on attention deficit hyperactivity disorder: A systematic review.

Kim Y, Cho I, Cho S J Ginseng Res. 2024; 48(5):437-448.

PMID: 39263306 PMC: 11385392. DOI: 10.1016/j.jgr.2024.05.006.

References

Detering N, Collins R, Hawkins R, Ozand P, Karahasan A . The effects of ethanol on developing catecholamine neurons. Adv Exp Med Biol. 1980; 132:721-7. DOI: 10.1007/978-1-4757-1419-7_75. View

van Lieshout M, Luman M, Twisk J, van Ewijk H, Groenman A, Thissen A . A 6-year follow-up of a large European cohort of children with attention-deficit/hyperactivity disorder-combined subtype: outcomes in late adolescence and young adulthood. Eur Child Adolesc Psychiatry. 2016; 25(9):1007-17. PMC: 4990613. DOI: 10.1007/s00787-016-0820-y. View

Johansen E, Aase H, Meyer A, Sagvolden T . Attention-deficit/hyperactivity disorder (ADHD) behaviour explained by dysfunctioning reinforcement and extinction processes. Behav Brain Res. 2002; 130(1-2):37-45. DOI: 10.1016/s0166-4328(01)00434-x. View

Faraone S, Perlis R, Doyle A, Smoller J, Goralnick J, Holmgren M . Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005; 57(11):1313-23. DOI: 10.1016/j.biopsych.2004.11.024. View

Xi T, Wu J . A Review on the Mechanism Between Different Factors and the Occurrence of Autism and ADHD. Psychol Res Behav Manag. 2021; 14:393-403. PMC: 8044340. DOI: 10.2147/PRBM.S304450. View

Jacobson J, Jacobson S . Intellectual impairment in children exposed to polychlorinated biphenyls in utero. N Engl J Med. 1996; 335(11):783-9. DOI: 10.1056/NEJM199609123351104. View

Gomez-Sanchez C, Riveiro-Alvarez R, Soto-Insuga V, Rodrigo M, Tirado-Requero P, Mahillo-Fernandez I . Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children. Behav Brain Funct. 2016; 12(1):2. PMC: 4706690. DOI: 10.1186/s12993-015-0084-6. View

Wagner-Schuman M, Richardson J, Auinger P, Braun J, Lanphear B, Epstein J . Association of pyrethroid pesticide exposure with attention-deficit/hyperactivity disorder in a nationally representative sample of U.S. children. Environ Health. 2015; 14:44. PMC: 4458051. DOI: 10.1186/s12940-015-0030-y. View

Rice D, Gilbert S . Lack of sensitive period for lead-induced behavioral impairment on a spatial delayed alternation task in monkeys. Toxicol Appl Pharmacol. 1990; 103(2):364-73. DOI: 10.1016/0041-008x(90)90236-n. View

10.

Cory-Slechta D . Relationships between Pb-induced changes in neurotransmitter system function and behavioral toxicity. Neurotoxicology. 1997; 18(3):673-88. View

11.

Diaz M, Jotty K, Locke J, Jones S, Valenzuela C . Moderate Alcohol Exposure during the Rat Equivalent to the Third Trimester of Human Pregnancy Alters Regulation of GABAA Receptor-Mediated Synaptic Transmission by Dopamine in the Basolateral Amygdala. Front Pediatr. 2014; 2:46. PMC: 4035091. DOI: 10.3389/fped.2014.00046. View

12.

Castellanos F, Giedd J, Marsh W, Hamburger S, Vaituzis A, Dickstein D . Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder. Arch Gen Psychiatry. 1996; 53(7):607-16. DOI: 10.1001/archpsyc.1996.01830070053009. View

13.

Sagvolden T, HENDLEY E, Knardahl S . Behavior of hypertensive and hyperactive rat strains: hyperactivity is not unitarily determined. Physiol Behav. 1992; 52(1):49-57. DOI: 10.1016/0031-9384(92)90432-2. View

14.

Rice D, Karpinski K . Lifetime low-level lead exposure produces deficits in delayed alternation in adult monkeys. Neurotoxicol Teratol. 1988; 10(3):207-14. DOI: 10.1016/0892-0362(88)90019-0. View

15.

Bushnell P, Moser V, MacPhail R, Oshiro W, Derr-Yellin E, Phillips P . Neurobehavioral assessments of rats perinatally exposed to a commercial mixture of polychlorinated biphenyls. Toxicol Sci. 2002; 68(1):109-20. DOI: 10.1093/toxsci/68.1.109. View

16.

Davis G, Stewart A, Stanwood G, Gowrishankar R, Hahn M, Blakely R . Functional coding variation in the presynaptic dopamine transporter associated with neuropsychiatric disorders drives enhanced motivation and context-dependent impulsivity in mice. Behav Brain Res. 2017; 337:61-69. PMC: 5645257. DOI: 10.1016/j.bbr.2017.09.043. View

17.

de Bruin N, Kiliaan A, de Wilde M, Broersen L . Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats. Neurobiol Learn Mem. 2003; 80(1):63-79. DOI: 10.1016/s1074-7427(03)00024-8. View

18.

Sourander A, Sucksdorff M, Chudal R, Surcel H, Hinkka-Yli-Salomaki S, Gyllenberg D . Prenatal Cotinine Levels and ADHD Among Offspring. Pediatrics. 2019; 143(3). PMC: 6398365. DOI: 10.1542/peds.2018-3144. View

19.

Barr A, Lehmann-Masten V, Paulus M, Gainetdinov R, Caron M, Geyer M . The selective serotonin-2A receptor antagonist M100907 reverses behavioral deficits in dopamine transporter knockout mice. Neuropsychopharmacology. 2003; 29(2):221-8. DOI: 10.1038/sj.npp.1300343. View

20.

Schantz S . Developmental neurotoxicity of PCBs in humans: what do we know and where do we go from here?. Neurotoxicol Teratol. 1996; 18(3):217-27; discussion 229-76. DOI: 10.1016/s0892-0362(96)90001-x. View