Hippocampal long-term potentiation is modulated by exercise-induced alterations in dopaminergic synaptic transmission in mice selectively bred for high voluntary wheel running

Abstract

Background

High-Runner (HR) mice, selectively bred for increased voluntary wheel running behavior, exhibit heightened motivation to run. Exercise has been shown to influence hippocampal long-term potentiation (LTP) and memory, and is neuroprotective in several neurodegenerative diseases.

Objective

This study aimed to determine the impact of intense running in HR mice with wheel access on hippocampal LTP, compared to HR mice without wheels and non-selected control (C) mice with/without wheels. Additionally, we investigated the involvement of D1/D5 receptors and the dopamine transporter (DAT) in LTP modulation and examined levels of these proteins in HR and C mice.

Methods

Adult female HR and C mice were individually housed with/without running wheels for at least two weeks. Hippocampal LTP of extracellular field excitatory postsynaptic potentials (fEPSPs) was measured in area CA1, and SKF-38393 (D1/D5 receptor agonist) and GBR 12909 (DAT inhibitor) were used to probe the role of D1/D5 receptors and DAT in LTP differences. Western blot analyses assessed D1/D5 receptor and DAT expression in the hippocampus, prefrontal cortex, and cerebellum.

Results

HR mice with wheel access showed significantly increased hippocampal LTP compared to those without wheels and to C mice with/without wheels. Treatment with SKF-38393 or GBR 12909 prevented the heightened LTP in HR mice with wheels, aligning it with levels in C mice. Hippocampal D1/D5 receptor levels were lower, and DAT levels were higher in HR mice compared to C mice. No significant changes were observed in other brain regions.

Conclusions

The increased hippocampal LTP seen in HR mice with wheel access may be related to alterations in dopaminergic synaptic transmission that underlie the neurophysiological basis of hyperactivity, motor disorders, and/or motivation.

Keywords

high-runner mice voluntary running long-term potentiation dopamine D1 receptors hippocampus

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References

Alomari

M. A.

Khabour

O. F.

Alzoubi

K. H.

Alzubi

M. A.

(2013). Forced and voluntary exercises equally improve spatial learning and memory and hippocampal BDNF levels. Behavioural Brain Research, 247, 34–39. https://doi.org/10.1016/j.bbr.2013.03.007

Arzate-Mejía

R. G.

Lottenbach

Schindler

Jawaid

Mansuy

I. M.

(2020). Long-term impact of social isolation and molecular underpinnings. Frontiers in Genetics, 11. https://doi.org/10.3389/fgene.2020.589621

Binda

K. H.

Lillethorup

T. P.

Real

C. C.

Bærentzen

S. L.

Nielsen

M. N.

Orlowski

Brooks

D. J.

Chacur

Landau

A. M.

(2021). Exercise protects synaptic density in a rat model of Parkinson’s disease. Experimental Neurology, 342, 113741. https://doi.org/10.1016/j.expneurol.2021.113741

Bronikowski

A. M.

Rhodes

J. S.

Garland

Jr. Prolla

T. A.

Awad

T. A.

Gammie

S. C.

(2004). The evolution of gene expression in mouse hippocampus in response to selective breeding for increased locomotor activity. Evolution, 58(9), 2079–2086. https://doi.org/10.1111/j.0014-3820.2004.tb00491.x

Caetano-Anollés

Rhodes

J. S.

Garland

Jr. Perez

S. D.

Hernandez

A. G.

Southey

B. R.

Rodriguez-Zas

S. L.

(2016). Cerebellum transcriptome of mice bred for high voluntary activity offers insights into locomotor control and reward-dependent behaviors. PLOS ONE, 11(11), e0167095. https://doi.org/10.1371/journal.pone.0167095

Careau

Wolak

M. E.

Carter

P. A.

Garland

Jr. (2013). Limits to behavioral evolution: The quantitative genetics of a complex trait under directional selection: Quantitative genetics of a selection limit. Evolution, 67(11), 3102–3119. https://doi.org/10.1111/evo.12200

Carek

P. J.

Laibstain

S. E.

Carek

S. M.

(2011). Exercise for the treatment of depression and anxiety. International Journal of Psychiatry in Medicine, 41(1), 15–28. https://doi.org/10.2190/PM.41.1.c

Challa

S. R.

Fornal

C. A.

Wang

B. C.

Boyineni

DeVera

R. E.

Unnam

Song

Soares

M. B.

Malchenko

Gyarmati

Veeravalli

K. K.

(2023). The impact of social isolation and environmental deprivation on blood pressure and depression-like behavior in young male and female mice. Chronic Stress, 7, 24705470231207010. https://doi.org/10.1177/24705470231207010

Chowdhury

Luchetti

Fernandes

Filho

D. A.

Kastellakis

Tzilivaki

Ramirez

E. M.

Tran

M. Y.

Poirazi

Silva

A. J

. (2022). A locus coeruleus-dorsal CA1 dopaminergic circuit modulates memory linking. Neuron, 110(20), 3374–3388. e8. https://doi.org/10.1016/j.neuron.2022.08.001

10.

Christie

B. R.

Eadie

B. D.

Kannangara

T. S.

Robillard

J. M.

Shin

Titterness

A. K.

(2008). Exercising our brains: How physical activity impacts synaptic plasticity in the dentate gyrus. NeuroMolecular Medicine, 10(2), 47–58. https://doi.org/10.1007/s12017-008-8033-2

11.

Cooper

Moon

H. Y.

van Praag

(2018). On the run for hippocampal plasticity. Cold Spring Harbor Perspectives in Medicine, 8(4), a029736. https://doi.org/10.1101/cshperspect.a029736

12.

Copes

L. E.

Schutz

Dlugosz

E. M.

Acosta

Chappell

M. A.

Garland

Jr. (2015). Effects of voluntary exercise on spontaneous physical activity and food consumption in mice: Results from an artificial selection experiment. Physiology & Behavior, 149, 86–94. https://doi.org/10.1016/j.physbeh.2015.05.025

13.

Czurkó

Hirase

Csicsvari

Buzsáki

(1999). Sustained activation of hippocampal pyramidal cells by ‘space clamping’ in a running wheel: Sustained discharge of hippocampal pyramidal cells. European Journal of Neuroscience, 11(1), 344–352. https://doi.org/10.1046/j.1460-9568.1999.00446.x

14.

da Costa Daniele

T. M.

de Bruin

P. F. C.

de Matos

R. S.

de Bruin

G. S.

Maia Chaves

de Bruin

V. M. S.

(2020). Exercise effects on brain and behavior in healthy mice, Alzheimer’s disease and Parkinson’s disease model—A systematic review and meta-analysis. Behavioural Brain Research, 383, 112488. https://doi.org/10.1016/j.bbr.2020.112488

15.

Dahlin

Andersson

Thorén

Hanse

Seth

(2019). Effects of physical exercise and stress on hippocampal CA1 and dentate gyrus synaptic transmission and long-term potentiation in adolescent and adult Wistar rats. Neuroscience, 408, 22–30. https://doi.org/10.1016/j.neuroscience.2019.03.046

16.

Dao

A. T.

Zagaar

M. A.

Levine

A. T.

Alkadhi

K. A.

(2016). Comparison of the effect of exercise on late-phase LTP of the dentate gyrus and CA1 of Alzheimer’s disease model. Molecular Neurobiology, 53(10), 6859–6868. https://doi.org/10.1007/s12035-015-9612-5

17.

da Silva

W. C. N.

Köhler

C. C.

Radiske

Cammarota

(2012). D1/D5 dopamine receptors modulate spatial memory formation. Neurobiology of Learning and Memory, 97(2), 271–275. https://doi.org/10.1016/j.nlm.2012.01.005

18.

Dong

T. N.

Kramar

E. A.

Beardwood

J. H.

Al-Shammari

Wood

M. A.

Keiser

(2022). Temporal endurance of exercise-induced benefits on hippocampus-dependent memory and synaptic plasticity in female mice. Neurobiology of Learning and Memory, 194, 107658. https://doi.org/10.1016/j.nlm.2022.107658

19.

Duman

C. H.

Schlesinger

Russell

D. S.

Duman

R. S.

(2008). Voluntary exercise produces antidepressant and anxiolytic behavioral effects in mice. Brain Research, 1199, 148–158. https://doi.org/10.1016/j.brainres.2007.12.047

20.

Duszkiewicz

A. J.

McNamara

C. G.

Takeuchi

Genzel

(2019). Novelty and dopaminergic modulation of memory persistence: A tale of two systems. Trends in Neurosciences, 42(2), 102–114. https://doi.org/10.1016/j.tins.2018.10.002

21.

Erickson

K. I.

Voss

M. W.

Prakash

R. S.

Basak

Szabo

Chaddock

Kim

J. S.

Heo

Alves

White

S. M.

Wojcicki

T. R.

Mailey

Vieira

V. J.

Martin

S. A.

Pence

B. D.

Woods

J. A.

McAuley

Kramer

A. F.

(2011). Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences, 108(7), 3017–3022. https://doi.org/10.1073/pnas.1015950108

22.

Ernst

Olson

A. K.

Pinel

J. P. J.

Lam

R. W.

Christie

B. R.

(2006). Antidepressant effects of exercise: Evidence for an adult-neurogenesis hypothesis? Journal of Psychiatry and Neuroscience, 31(2), 84–92. PMID: 16575423

23.

Farmer

Zhao

van Praag

Wodtke

Gage

F. H.

Christie

B. R.

(2004). Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male sprague–dawley rats in vivo. Neuroscience, 124(1), 71–79. https://doi.org/10.1016/j.neuroscience.2003.09.029

24.

Fordyce

D. E.

Wehner

J. M.

(1993). Physical activity enhances spatial learning performance with an associated alteration in hippocampal protein kinase C activity in C57BL/6 and DBA/2 mice. Brain Research, 619(1–2), 111–119. https://doi.org/10.1016/0006-8993(93)91602-O

25.

Frey

Schroeder

Matthies

(1990). Dopaminergic antagonists prevent long-term maintenance of posttetanic LTP in the CA1 region of rat hippocampal slices. Brain Research, 522(1), 69–75. https://doi.org/10.1016/0006-8993(90)91578-5

26.

Fuss

Ben Abdallah

N. M.-B.

Vogt

M. A.

Touma

Pacifici

P. G.

Palme

Witzemann

Hellweg

Gass

(2010). Voluntary exercise induces anxiety-like behavior in adult C57BL/6J mice correlating with hippocampal neurogenesis. Hippocampus, 20(3), 364–376. https://doi.org/10.1002/hipo.20634

27.

Gaitán

J. M.

Moon

H. Y.

Stremlau

Dubal

D. B.

Cook

D. B.

Okonkwo

O. C.

van Praag

(2021). Effects of Aerobic Exercise Training on Systemic Biomarkers and Cognition in Late Middle-Aged Adults at Risk for Alzheimer’s Disease. Frontiers in Endocrinology, 12. https://doi.org/10.3389/fendo.2021.660181

28.

Gangarossa

Longueville

De Bundel

Perroy

Hervé

Girault

J.-A.

Valjent

(2012). Characterization of dopamine D1 and D2 receptor-expressing neurons in the mouse hippocampus. Hippocampus, 22(12), 2199–2207. https://doi.org/10.1002/hipo.22044

29.

Garland

Jr. Schutz

Chappell

M. A.

Keeney

B. K.

Meek

T. H.

Copes

L. E.

Acosta

Drenowatz

Maciel

R. C.

van Dijk

Kotz

C. M.

Eisenmann

J. C.

(2011). The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: Human and rodent perspectives. Journal of Experimental Biology, 214(2), 206–229. https://doi.org/10.1242/jeb.048397

30.

Girard

McAleer

M. W.

Rhodes

J. S.

Garland

Jr. (2001). Selection for high voluntary wheel-running increases speed and intermittency in house mice (Mus domesticus). Journal of Experimental Biology, 204(24), 4311–4320. https://doi.org/10.1242/jeb.204.24.4311

31.

Hansen

Manahan-Vaughan

(2014). Dopamine D1/D5 receptors mediate informational saliency that promotes persistent hippocampal long-term plasticity. Cerebral Cortex, 24(4), 845–858. https://doi.org/10.1093/cercor/bhs362

32.

Hillis

D. A.

Yadgary

Weinstock

G. M.

Pardo-Manuel de Villena

Pomp

Fowler

A. S.

Chan

Garland

Jr. (2020). Genetic basis of aerobically supported voluntary exercise: Results from a selection experiment with house mice. Genetics, 216(3), 781–804. https://doi.org/10.1534/genetics.120.303668

33.

Hillman

C. H.

Erickson

K. I.

Kramer

A. F.

(2008). Be smart, exercise your heart: Exercise effects on brain and cognition.

34.

Huuha

A. M.

Norevik

C. S.

Moreira

J. B. N.

Kobro-Flatmoen

Scrimgeour

Kivipelto

Praag

H. V.

Ziaei

Sando

S. B.

Wisløff

Tari

A. R.

(2022). Can exercise training teach US how to treat Alzheimer’s disease? Ageing Research Reviews, 75. https://doi.org/10.1016/j.arr.2022.101559

35.

Ingram

D. K.

(2000). Age-related decline in physical activity: Generalization to nonhumans. Medicine & Science in Sports & Exercise, 32(9), 1623. https://doi.org/10.1097/00005768-200009000-00016

36.

Jahangiri

Gholamnezhad

Hosseini

(2019). Neuroprotective effects of exercise in rodent models of memory deficit and Alzheimer’s. Metabolic Brain Disease, 34(1), 21–37. https://doi.org/10.1007/s11011-018-0343-y

37.

Johnson

R. A.

Rhodes

J. S.

Jeffrey

S. L.

Garland

Jr. , & Mitchell

G. S.

(2003). Hippocampal brain-derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running. Neuroscience, 121(1), 1–7. https://doi.org/10.1016/S0306-4522(03)00422-6

38.

Kang

Welcher

A. A.

Shelton

Schuman

E. M.

(1997). Neurotrophins and time: Different roles for TrkB signaling in hippocampal long-term potentiation. Neuron, 19(3), 653–664. https://doi.org/10.1016/S0896-6273(00)80378-5

39.

Kantak

K. M.

(2022). Rodent models of attention-deficit hyperactivity disorder: An updated framework for model validation and therapeutic drug discovery. Pharmacology Biochemistry and Behavior, 216, 173378. https://doi.org/10.1016/j.pbb.2022.173378

40.

Kempadoo

K. A.

Mosharov

E. V.

Choi

S. J.

Sulzer

Kandel

E. R.

(2016). Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory. Proceedings of the National Academy of Sciences, 113(51), 14835–14840. https://doi.org/10.1073/pnas.1616515114

41.

Khan

R. H.

Rhodes

J. S.

Girard

I. A.

Schwartz

N. E.

Garland

Jr. (2024). Does behavior evolve first? Correlated responses to selection for voluntary wheel-running behavior in house mice. Ecological and Evolutionary Physiology, 97(2), 97–117. https://doi.org/10.1086/730153

42.

Knab

A. M.

Bowen

R. S.

Hamilton

A. T.

Gulledge

A. A.

Lightfoot

J. T.

(2009). Altered dopaminergic profiles: Implications for the regulation of voluntary physical activity. Behavioural Brain Research, 204(1), 147–152. https://doi.org/10.1016/j.bbr.2009.05.034

43.

Kobilo

Liu

Q.-R.

Gandhi

Mughal

Shaham

van Praag

(2011). Running is the neurogenic and neurotrophic stimulus in environmental enrichment. Learning & Memory, 18(9), 605–609. https://doi.org/10.1101/lm.2283011

44.

Koob

G. F.

Volkow

N. D.

(2010). Neurocircuitry of addiction. Neuropsychopharmacology, 35(1), 217–238. https://doi.org/10.1038/npp.2009.110

45.

Kramár

E. A.

Lin

C.-Y.

Arai

A. C.

Gall

C. M.

Lynch

(2004). A novel mechanism for the facilitation of theta-induced long-term potentiation by brain-derived neurotrophic factor. The Journal of Neuroscience, 24(22), 5151–5161. https://doi.org/10.1523/JNEUROSCI.0800-04.2004

46.

Levey

A. I.

Hersch

S. M.

Rye

D. B.

Sunahara

R. K.

Niznik

H. B.

Kitt

C. A.

Price

D. L.

Maggio

Brann

M. R.

Ciliax

B. J.

(1993). Localization of D1 and D2 dopamine receptors in brain with subtype-specific antibodies. Proceedings of the National Academy of Sciences, 90(19), 8861–8865. https://doi.org/10.1073/pnas.90.19.8861

47.

Cullen

W. K.

Anwyl

Rowan

M. J.

(2003). Dopamine-dependent facilitation of LTP induction in hippocampal CA1 by exposure to spatial novelty. Nature Neuroscience, 6(5), 526–531. https://doi.org/10.1038/nn1049

48.

Lin

T.-W.

Tsai

S.-F.

Kuo

Y.-M.

(2018). Physical exercise enhances neuroplasticity and delays Alzheimer’s disease. Brain Plasticity, 4(1), 95–110. https://doi.org/10.3233/BPL-180073

49.

Lisman

J. E.

Grace

A. A.

(2005). The hippocampal-VTA loop: Controlling the entry of information into long-term memory. Neuron, 46(5), 703–713. https://doi.org/10.1016/j.neuron.2005.05.002

50.

Loprinzi

P. D.

(2019). The Effects of Exercise on Long-Term Potentiation: A Candidate Mechanism of the Exercise-Memory Relationship. OBM Neurobiology, 3(2). https://doi.org/10.21926/obm.neurobiol.1902026

51.

Madison

D. V.

Edson

E. B

. (1997). Preparation of hippocampal brain slices. Current Protocols in Neuroscience, (1). https://doi.org/10.1002/0471142301.ns0604s00

52.

Malisch

J. L.

Breuner

C. W.

Kolb

E. M.

Wada

Hannon

R. M.

Chappell

M. A.

Middleton

K. M.

Garland

Jr. (2009). Behavioral despair and home-cage activity in mice with chronically elevated baseline corticosterone concentrations. Behavior Genetics, 39(2), 192–201. https://doi.org/10.1007/s10519-008-9246-8

53.

Malisch

J. L.

Saltzman

Gomes

F. R.

Rezende

E. L.

Jeske

D. R.

Garland

Jr. (2007). Baseline and Stress-Induced Plasma Corticosterone Concentrations of Mice Selectively Bred for High Voluntary Wheel Running .

54.

Marck

Berthelot

Foulonneau

Marc

Antero-Jacquemin

Noirez

Bronikowski

A. M.

Morgan

T. J.

Garland

Jr. Carter

P. A.

Hersen

Di Meglio

J.-M.

Toussaint

J.-F.

(2016). Age-Related changes in locomotor performance reveal a similar pattern for Caenorhabditis elegans, Mus domesticus, Canis familiaris, Equus caballus, and Homo sapiens. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, glw136. https://doi.org/10.1093/gerona/glw136

55.

Mathes

W. F.

Nehrenberg

D. L.

Gordon

Hua

Garland

Jr. Pomp

(2010). Dopaminergic dysregulation in mice selectively bred for excessive exercise or obesity. Behavioural Brain Research, 210(2), 155–163. https://doi.org/10.1016/j.bbr.2010.02.016

56.

McNamara

C. G.

Tejero-Cantero

Trouche

Campo-Urriza

Dupret

(2014). Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence. Nature Neuroscience, 17(12), 1658–1660. https://doi.org/10.1038/nn.3843

57.

Mockett

B. G.

Brooks

W. M.

Tate

W. P.

Abraham

W. C.

(2004). Dopamine D1/D5 receptor activation fails to initiate an activity-independent late-phase LTP in rat hippocampus. Brain Research, 1021(1), 92–100. https://doi.org/10.1016/j.brainres.2004.06.039

58.

Mul

J. D.

Soto

Cahill

M. E.

Ryan

R. E.

Takahashi

Zheng

Croote

D. E.

Hirshman

M. F.

la Fleur

S. E.

Nestler

E. J.

Goodyear

L. J.

(2018). Voluntary wheel running promotes resilience to chronic social defeat stress in mice: A role for nucleus accumbens ΔFosB. Neuropsychopharmacology, 43(9), 1934–1942. https://doi.org/10.1038/s41386-018-0103-z

59.

Nestler

E. J.

Barrot

Self

D. W.

(2001). Δfosb: A sustained molecular switch for addiction. Proceedings of the National Academy of Sciences of the United States of America, 98(20), 11042–11046. https://doi.org/10.1073/pnas.191352698

60.

Nowacka-Chmielewska

Grabowska

Grabowski

Meybohm

Burek

Małecki

(2022). Running from stress: Neurobiological mechanisms of exercise-induced stress resilience. International Journal of Molecular Sciences, 23, 21. Article 21. https://doi.org/10.3390/ijms232113348

61.

O’Carroll

C. M.

Martin

S. J.

Sandin

Frenguelli

Morris

R. G. M.

(2006). Dopaminergic modulation of the persistence of one-trial hippocampus-dependent memory. Learning & Memory, 13(6), 760–769. https://doi.org/10.1101/lm.321006

62.

Otmakhova

N. A.

Lisman

J. E.

(1996). D1/D5 dopamine receptor activation increases the magnitude of early long-term potentiation at CA1 hippocampal synapses. The Journal of Neuroscience, 16(23), 7478–7486. https://doi.org/10.1523/JNEUROSCI.16-23-07478.1996

63.

Papaleonidopoulos

Kouvaros

Papatheodoropoulos

(2018). Effects of endogenous and exogenous D1/D5 dopamine receptor activation on LTP in ventral and dorsal CA1 hippocampal synapses. Synapse, 72(8), e22033. https://doi.org/10.1002/syn.22033

64.

Pietrelli

Matković

Vacotto

Lopez-Costa

J. J.

Basso

Brusco

(2018). Aerobic exercise upregulates the BDNF-serotonin systems and improves the cognitive function in rats. Neurobiology of Learning and Memory, 155, 528–542. https://doi.org/10.1016/j.nlm.2018.05.007

65.

Puighermanal

Cutando

Boubaker-Vitre

Honoré

Longueville

Hervé

Valjent

(2017). Anatomical and molecular characterization of dopamine D1 receptor-expressing neurons of the mouse CA1 dorsal hippocampus. Brain Structure and Function, 222(4), 1897–1911. https://doi.org/10.1007/s00429-016-1314-x

66.

Regan

S. L.

Williams

M. T.

Vorhees

C. V.

(2022). Review of rodent models of attention deficit hyperactivity disorder. Neuroscience & Biobehavioral Reviews, 132, 621–637. https://doi.org/10.1016/j.neubiorev.2021.11.041

67.

Rendeiro

Rhodes

J. S.

(2018). A new perspective of the hippocampus in the origin of exercise–brain interactions. Brain Structure and Function, 223(6), 2527–2545. https://doi.org/10.1007/s00429-018-1665-6

68.

Renoir

Pang

T. Y.

Zajac

M. S.

Chan

Leang

Chevarin

Lanfumey

Hannan

A. J.

(2012). Treatment of depressive-like behaviour in Huntington’s disease mice by chronic sertraline and exercise. British Journal of Pharmacology, 165(5), 1375–1389. https://doi.org/10.1111/j.1476-5381.2011.01567.x

69.

Rhodes

J. S.

Gammie

S. C.

Garland

Jr. (2005). Neurobiology of mice selected for high voluntary wheel-running activity. Integrative and Comparative Biology, 45(3), 438–455. https://doi.org/10.1093/icb/45.3.438

70.

Rhodes

J. S.

Garland

Jr. (2003). Differential sensitivity to acute administration of Ritalin, apormorphine, SCH 23390, but not raclopride in mice selectively bred for hyperactive wheel-running behavior. Psychopharmacology, 167(3), 242–250. https://doi.org/10.1007/s00213-003-1399-9

71.

Rhodes

J. S.

Garland

Jr. Gammie

S. C.

(2003a). Patterns of brain activity associated with variation in voluntary wheel-running behavior. Behavioral Neuroscience, 117(6), 1243–1256. https://doi.org/10.1037/0735-7044.117.6.1243

72.

Rhodes

J. S.

Hosack

Girard

Kelley

Mitchell

G. S.

Garland

Jr. (2001). Differential sensitivity to acute administration of cocaine, GBR 12909, and fluoxetine in mice selectively bred for hyperactive wheel-running behavior. Psychopharmacology, 158(2), 120–131. https://doi.org/10.1007/s002130100857

73.

Rhodes

J. S.

van Praag

Jeffrey

Girard

Mitchell

G. S.

Garland

Jr. Gage

F. H.

(2003b). Exercise increases hippocampal neurogenesis to high levels but does not improve spatial learning in mice bred for increased voluntary wheel running. Behavioral Neuroscience, 117(5), 1006–1016. https://doi.org/10.1037/0735-7044.117.5.1006

74.

Roberts

M. D.

Ruegsegger

G. N.

Brown

J. D.

Booth

F. W.

(2017). Mechanisms Associated With Physical Activity Behavior: Insights From Rodent Experiments .

75.

Roberts

M. D.

Toedebusch

R. G.

Wells

K. D.

Company

J. M.

Brown

J. D.

Cruthirds

C. L.

Heese

A. J.

Zhu

Rottinghaus

G. E.

Childs

T. E.

Booth

F. W.

(2014). Nucleus accumbens neuronal maturation differences in young rats bred for low versus high voluntary running behaviour. The Journal of Physiology, 592(10), 2119–2135. https://doi.org/10.1113/jphysiol.2013.268805

76.

Salam

J. N.

Fox

J. H.

DeTroy

E. M.

Guignon

M. H.

Wohl

D. F.

Falls

W. A.

(2009). Voluntary exercise in C57 mice is anxiolytic across several measures of anxiety. Behavioural Brain Research, 197(1), 31–40. https://doi.org/10.1016/j.bbr.2008.07.036

77.

Salyer

Lesousky

Weinman

E. J.

Clark

B. J.

Lederer

E. D.

Khundmiri

S. J.

(2011). Dopamine regulation of Na+-K+-ATPase requires the PDZ-2 domain of sodium hydrogen regulatory factor-1 (NHERF-1) in opossum kidney cells. American Journal of Physiology-Cell Physiology, 300(3), C425–C434. https://doi.org/10.1152/ajpcell.00357.2010

78.

Saul

M. C.

Majdak

Perez

Reilly

Garland

Jr. Rhodes

J. S.

(2017). High motivation for exercise is associated with altered chromatin regulators of monoamine receptor gene expression in the striatum of selectively bred mice. Genes, Brain and Behavior, 16(3), 328–341. https://doi.org/10.1111/gbb.12347

79.

Schmill

M. P.

Cadney

M. D.

Thompson

Hiramatsu

Albuquerque

R. L.

McNamara

M. P.

Castro

A. A.

Kay

J. C.

Buenaventura

D. G.

Ramirez

J. L.

Rhodes

J. S.

Garland

Jr. (2021). Conditioned place preference for cocaine and methylphenidate in female mice from lines selectively bred for high voluntary wheel-running behavior. Genes, Brain and Behavior, 20(2), e12700. https://doi.org/10.1111/gbb.12700

80.

Schmill

M. P.

Thompson

Lee

Haddadin

Mitra

Ezzat

Shelton

Levin

Benham

Huffman

K. J.

Garland

Jr. (2023). Hippocampal, whole midbrain, red nucleus, and ventral tegmental area volumes are increased by selective breeding for high voluntary wheel-running behavior. Brain Behav Evol, 98(5), 245–263. https://doi.org/10.1159/000533524

81.

Sriram

Pai

K. S.

Ravindranath

(2002). Protection and potentiation of 1-methyl-4-phenylpyridinium-induced toxicity by cytochrome P450 inhibitors and inducer may be due to the altered uptake of the toxin. Journal of Neurochemistry, 64(3), 1203–1208. https://doi.org/10.1046/j.1471-4159.1995.64031203.x

82.

Stojanovic

Orlova

Sialana

F. J.

Höger

Stuchlik

Milenkovic

Aradska

Lubec

(2017). Validation of dopamine receptor DRD1 and DRD2 antibodies using receptor deficient mice. Amino Acids, 49(6), 1101–1109. https://doi.org/10.1007/s00726-017-2408-3

83.

Stranahan

A. M.

Khalil

Gould

(2007). Running induces widespread structural alterations in the hippocampus and entorhinal cortex. Hippocampus, 17(11), 1017–1022. https://doi.org/10.1002/hipo.20348

84.

Swallow

J. G.

Carter

P. A.

Garland

Jr. (1998). Artificial selection for increased wheel-running behavior in house mice. Behavior Genetics, 28(3), 227–237. https://doi.org/10.1023/a:1021479331779

85.

Swanson-Park

J. L.

Coussens

C. M.

Mason-Parker

S. E.

Raymond

C. R.

Hargreaves

E. L.

Dragunow

Cohen

A. S.

Abraham

W. C.

(1999). A double dissociation within the hippocampus of dopamine D1/D5 receptor and β-adrenergic receptor contributions to the persistence of long-term potentiation. Neuroscience, 92(2), 485–497. https://doi.org/10.1016/S0306-4522(99)00010-X

86.

Szasz

B. K.

Vizi

E. S.

Kiss

J. P.

(2007). Nicotinic acetylcholine receptor antagonistic property of the selective dopamine uptake inhibitor, GBR-12909 in rat hippocampal slices. Neuroscience, 145(1), 344–349. https://doi.org/10.1016/j.neuroscience.2006.11.032

87.

Takeuchi

Duszkiewicz

A. J.

Sonneborn

Spooner

P. A.

Yamasaki

Watanabe

Smith

C. C.

Fernández

Deisseroth

Greene

R. W.

Morris

R. G. M.

(2016). Locus coeruleus and dopaminergic consolidation of everyday memory. Nature, 537(7620), 357–362. https://doi.org/10.1038/nature19325

88.

Thapar

Cooper

(2016). Attention deficit hyperactivity disorder. The Lancet, 387(10024), 1240–1250. https://doi.org/10.1016/S0140-6736(15)00238-X

89.

van Praag

Christie

B. R.

Sejnowski

T. J.

Gage

F. H.

(1999). Running enhances neurogenesis, learning, and long-term potentiation in mice. Proceedings of the National Academy of Sciences, 96(23), 13427–13431. https://doi.org/10.1073/pnas.96.23.13427

90.

van Praag

Shubert

Zhao

Gage

F. H.

(2005). Exercise enhances learning and hippocampal neurogenesis in aged mice. The Journal of Neuroscience, 25(38), 8680–8685. https://doi.org/10.1523/JNEUROSCI.1731-05.2005

91.

Vints

W. A. J.

Levin

Fujiyama

Verbunt

Masiulis

(2022). Exerkines and long-term synaptic potentiation: Mechanisms of exercise-induced neuroplasticity. Frontiers in Neuroendocrinology, 66, 100993. https://doi.org/10.1016/j.yfrne.2022.100993

92.

Wallace

I. J.

Garland

Jr. (2016). Mobility as an emergent property of biological organization: Insights from experimental evolution: Mobility and biological organization. Evolutionary Anthropology: Issues, News, and Reviews, 25(3), 98–104. https://doi.org/10.1002/evan.21481

93.

Waters

R. P.

Pringle

R. B.

Forster

G. L.

Renner

K. J.

Malisch

J. L.

Garland

Jr. Swallow

J. G.

(2013). Selection for increased voluntary wheel-running affects behavior and brain monoamines in mice. Brain Research, 1508, 9–22. https://doi.org/10.1016/j.brainres.2013.01.033

94.

Wikgren

Mertikas

G. G.

Raussi

Tirkkonen

Äyräväinen

Pelto-Huikko

Koch

L. G.

Britton

S. L.

Kainulainen

(2012). Selective breeding for endurance running capacity affects cognitive but not motor learning in rats.

95.

Yamasaki

Takeuchi

(2017). Locus coeruleus and dopamine-dependent memory consolidation. Neural Plasticity, 2017, 1–15. https://doi.org/10.1155/2017/8602690

96.

Zhang

McCarthy

D. M.

Sharma

Bhide

P. G.

(2015). Dopamine receptor and gα(olf) expression in DYT1 dystonia mouse models during postnatal development. PLOS ONE, 10(4), e0123104. https://doi.org/10.1371/journal.pone.0123104

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