Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Neurological Sciences
Published in: Neurological Sciences 3/2022

01-03-2022 | Addiction | Review Article

Addiction-induced plasticity in underlying neural circuits

Authors: Masoumeh Kourosh-Arami, Alireza Komaki, Masoumeh Gholami

Published in: Neurological Sciences | Issue 3/2022

Login to get access

Abstract

Synaptic plasticity, the substrate for learning, has been established in neural reward circuits and might involve in the learning of addictive behaviors. Long-term exposure to addictive drugs caused long-lasting memories of the drug experience. The main clinical problem that involves the persistence of addiction is a relapse that is resulted from the exposure to cues of the drug experience. Persistent forms of synaptic plasticity are associated with some of the behavioral effects of addictive drugs. Here, we present the underlying mechanisms of plasticity induced by different brain reward circuitry. Therefore, we focus on the collected evidence that drugs of abuse can disturb synaptic plasticity in the main brain circuits of addiction. Prevention of these drug-induced synaptic modifications may be helpful in the treatment of this problem of society.
Literature
1.
Grzęda E, Wiśniewska RJ (2008) Differentiations of the effect of NMDA on the spatial learning of rats with 4 and 12 week diabetes mellitus. Acta Neurobiol Exp 68:398œ406
2.
Heidari MH et al (2013) Effect of chronic morphine consumption on synaptic plasticity of rat’s hippocampus: a transmission electron microscopy study. Neurol Res Int 2013
3.
Hyman SE, Malenka RC (2001) Addiction and the brain: the neurobiology of compulsion and its persistence. Nat Rev Neurosci 2(10):695–703PubMedCrossRef
4.
Hyman SE, Malenka RC, Nestler EJ (2006) Neural mechanisms of addiction: the role of reward-related learning and memory. Annu Rev Neurosci 29:565–598PubMedCrossRef
5.
Kalivas PW, Volkow ND (2005) The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 162(8):1403–1413PubMedCrossRef
6.
Montague PR, Hyman SE, Cohen JD (2004) Computational roles for dopamine in behavioural control. Nature 431(7010):760–767PubMedCrossRef
7.
Kelley AE (2004) Memory and addiction: shared neural circuitry and molecular mechanisms. Neuron 44(1):161–179PubMedCrossRef
8.
9.
Alcantara AA et al (2011) Cocaine-and morphine-induced synaptic plasticity in the nucleus accumbens. Synapse 65(4):309–320PubMedCrossRef
10.
11.
Wolf ME (2002) Addiction: making the connection between behavioral changes and neuronal plasticity in specific pathways. Mol Interv 2(3):146PubMedCrossRef
12.
Luscher C, Malenka R (2011) Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit remodeling. Neuron 69:650e663CrossRef
13.
Thomas MJ et al (2001) Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nat Neurosci 4(12):1217–1223PubMedCrossRef
14.
15.
16.
17.
18.
Shen H et al (2011) Heroin relapse requires long-term potentiation-like plasticity mediated by NMDA2b-containing receptors. Proc Natl Acad Sci 108(48):19407–19412PubMedPubMedCentralCrossRef
19.
Foeller E, Feldman DE (2004) Synaptic basis for developmental plasticity in somatosensory cortex. Curr Opin Neurobiol 14(1):89–95PubMedCrossRef
20.
Mansvelder HD, McGehee DS (2000) Long-term potentiation of excitatory inputs to brain reward areas by nicotine. Neuron 27(2):349–357PubMedCrossRef
21.
22.
Bellone C, Lüscher C (2005) mGluRs induce a long-term depression in the ventral tegmental area that involves a switch of the subunit composition of AMPA receptors. Eur J Neurosci 21(5):1280–1288PubMedCrossRef
23.
24.
Harris G et al (2004) Glutamate-associated plasticity in the ventral tegmental area is necessary for conditioning environmental stimuli with morphine. Neuroscience 129(3):841–847PubMedCrossRef
25.
Harris GC, Aston-Jones G (2003) Critical role for ventral tegmental glutamate in preference for a cocaine-conditioned environment. Neuropsychopharmacology 28(1):73–76PubMedCrossRef
26.
27.
Scofield M et al (2016) The nucleus accumbens: mechanisms of addiction across drug classes reflect the importance of glutamate homeostasis. Pharmacol Rev 68(3):816–871PubMedPubMedCentralCrossRef
28.
Bossert JM, Busch RF, Gray SM (2005) The novel mGluR2/3 agonist LY379268 attenuates cue-induced reinstatement of heroin seeking. NeuroReport 16(9):1013–1016PubMedCrossRef
29.
Bossert JM et al (2006) The mGluR2/3 agonist LY379268 attenuates context-and discrete cue-induced reinstatement of sucrose seeking but not sucrose self-administration in rats. Behav Brain Res 173(1):148–152PubMedCrossRef
30.
Khaleghzadeh-Ahangar H, Haghparast A (2015) Intra-accumbal CB1 receptor blockade reduced extinction and reinstatement of morphine. Physiol Behav 149:212–219PubMedCrossRef
31.
Kruyer A, Chioma VC, Kalivas PW (2020) The opioid-addicted tetrapartite synapse. Biol Psychiatry 87(1):34–43PubMedCrossRef
32.
Yuan K et al (2017) Morphine treatment enhances glutamatergic input onto neurons of the nucleus accumbens via both disinhibitory and stimulating effect. Addict Biol 22(6):1756–1767PubMedCrossRef
33.
Chidambaram SB et al (2019) Dendritic spines: revisiting the physiological role. Prog Neuropsychopharmacol Biol Psychiatry 92:161–193PubMedCrossRef
34.
Williams SR, Stuart GJ (2003) Role of dendritic synapse location in the control of action potential output. Trends Neurosci 26(3):147–154PubMedCrossRef
35.
Sjostrom PJ et al (2008) Dendritic excitability and synaptic plasticity. Physiol Rev 88(2):769–840PubMedCrossRef
36.
Beckerman MA, Ogorodnik E, Glass MJ (2013) Acute morphine associated alterations in the subcellular location of the AMPA-GluR1 receptor subunit in dendrites of neurons in the mouse central nucleus of the amygdala: comparisons and contrasts with other glutamate receptor subunits. Synapse 67(10):692–704PubMedPubMedCentralCrossRef
37.
38.
Koob GF, Maldonado R, Stinus L (1992) Neural substrates of opiate withdrawal. Trends Neurosci 15(5):186–191PubMedCrossRef
39.
40.
Maisonneuve IM, Ho A, Kreek MJ (1995) Chronic administration of a cocaine “binge” alters basal extracellular levels in male rats: an in vivo microdialysis study. J Pharmacol Exp Ther 272(2):652–657PubMed
41.
Volkow N et al (1997) Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature 386(6627):830–833PubMedCrossRef
42.
Kauer JA (2004) Learning mechanisms in addiction: synaptic plasticity in the ventral tegmental area as a result of exposure to drugs of abuse. Annu Rev Physiol 66:447–475PubMedCrossRef
43.
44.
45.
Langleben DD et al (2008) Acute effect of methadone maintenance dose on brain FMRI response to heroin-related cues. Am J Psychiatry 165(3):390–394PubMedCrossRef
46.
Luigjes JV et al (2012) Deep brain stimulation in addiction: a review of potential brain targets. Mol Psychiatry 17(6):572–583PubMedCrossRef
47.
Müller UJ et al (2013) Deep brain stimulation of the nucleus accumbens for the treatment of addiction. Ann N Y Acad Sci 1282(1):119–128PubMedCrossRef
48.
49.
Ungless MA et al (2001) Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 411(6837):583–587PubMedCrossRef
50.
Saal D et al (2003) Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron 37(4):577–582PubMedCrossRef
51.
Fitzgerald LW et al (1996) Drugs of abuse and stress increase the expression of GluR1 and NMDAR1 glutamate receptor subunits in the rat ventral tegmental area: common adaptations among cross-sensitizing agents. J Neurosci 16(1):274–282PubMedPubMedCentralCrossRef
52.
Mameli M et al (2009) Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the NAc. Nat Neurosci 12(8):1036–1041PubMedCrossRef
53.
Yuan T et al (2013) Expression of cocaine-evoked synaptic plasticity by GluN3A-containing NMDA receptors. Neuron 80(4):1025–1038PubMedCrossRef
54.
Niehaus JL, Murali M, Kauer JA (2010) Drugs of abuse and stress impair LTP at inhibitory synapses in the ventral tegmental area. Eur J Neurosci 32(1):108–117PubMedPubMedCentralCrossRef
55.
56.
Mansvelder HD, Keath JR, McGehee DS (2002) Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas. Neuron 33(6):905–919PubMedCrossRef
57.
Nugent FS, Penick EC, Kauer JA (2007) Opioids block long-term potentiation of inhibitory synapses. Nature 446(7139):1086–1090PubMedCrossRef
58.
Bocklisch C et al (2013) Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area. Science 341(6153):1521–1525PubMedCrossRef
59.
60.
Groenewegen HJ et al (1999) Convergence and segregation of ventral striatal inputs and outputs. Ann N Y Acad Sci 877(1):49–63PubMedCrossRef
61.
Pierce RC et al (1996) Repeated cocaine augments excitatory amino acid transmission in the nucleus accumbens only in rats having developed behavioral sensitization. J Neurosci 16(4):1550–1560PubMedPubMedCentralCrossRef
62.
Yao W-D et al (2004) Identification of PSD-95 as a regulator of dopamine-mediated synaptic and behavioral plasticity. Neuron 41(4):625–638PubMedCrossRef
63.
Boudreau AC, Wolf ME (2005) Behavioral sensitization to cocaine is associated with increased AMPA receptor surface expression in the nucleus accumbens. J Neurosci 25(40):9144–9151PubMedPubMedCentralCrossRef
64.
65.
66.
Ping A et al (2008) Contributions of nucleus accumbens core and shell GluR1 containing AMPA receptors in AMPA-and cocaine-primed reinstatement of cocaine-seeking behavior. Brain Res 1215:173–182PubMedPubMedCentralCrossRef
67.
68.
Sutton MA et al (2003) Extinction-induced upregulation in AMPA receptors reduces cocaine-seeking behaviour. Nature 421(6918):70–75PubMedCrossRef
69.
70.
Bajo M et al (2011) Neuroadaptation of GABAergic transmission in the central amygdala during chronic morphine treatment. Addict Biol 16(4):551–564PubMedCrossRef
71.
Kang-Park M-H et al (2009) μ-Opioid receptors selectively regulate basal inhibitory transmission in the central amygdala: lack of ethanol interactions. J Pharmacol Exp Ther 328(1):284–293PubMedCrossRef
72.
Finnegan TF, Chen S-R, Pan H-L (2005) Effect of the μ opioid on excitatory and inhibitory synaptic inputs to periaqueductal gray-projecting neurons in the amygdala. J Pharmacol Exp Ther 312(2):441–448PubMedCrossRef
73.
Gabbott PL et al (2005) Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers. J Comp Neurol 492(2):145–177PubMedCrossRef
74.
Hoover WB, Vertes RP (2007) Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat. Brain Struct Funct 212(2):149–179PubMedCrossRef
75.
Van den Oever MC et al (2008) Prefrontal cortex AMPA receptor plasticity is crucial for cue-induced relapse to heroin-seeking. Nat Neurosci 11(9):1053–1058PubMedCrossRef
76.
Sun W, Rebec GV (2006) Repeated cocaine self-administration alters processing of cocaine-related information in rat prefrontal cortex. J Neurosci 26(30):8004–8008PubMedPubMedCentralCrossRef
77.
Gipson CD, Kupchik YM, Kalivas PW (2014) Rapid, transient synaptic plasticity in addiction. Neuropharmacology 76:276–286PubMedCrossRef
78.
Peters J, LaLumiere RT, Kalivas PW (2008) Infralimbic prefrontal cortex is responsible for inhibiting cocaine seeking in extinguished rats. J Neurosci 28(23):6046–6053PubMedPubMedCentralCrossRef
79.
Lu H et al (2010) Elevated BDNF after cocaine withdrawal facilitates LTP in medial prefrontal cortex by suppressing GABA inhibition. Neuron 67(5):821–833PubMedPubMedCentralCrossRef
80.
Turrigiano GG (1999) Homeostatic plasticity in neuronal networks: the more things change, the more they stay the same. Trends Neurosci 22(5):221–227PubMedCrossRef
81.
Kogan JH, Nestler EJ, Aghajanian GK (1992) Elevated basal firing rates and enhanced responses to 8-Br-cAMP in locus coeruleus neurons in brain slices from opiate-dependent rats. Eur J Pharmacol 211(1):47–53PubMedCrossRef
82.
Dong Y et al (2006) CREB modulates excitability of nucleus accumbens neurons. Nat Neurosci 9(4):475–477PubMedCrossRef
83.
84.
Mazei-Robison MS et al (2011) Role for mTOR signaling and neuronal activity in morphine-induced adaptations in ventral tegmental area dopamine neurons. Neuron 72(6):977–990PubMedPubMedCentralCrossRef
85.
Bosch M, Hayashi Y (2012) Structural plasticity of dendritic spines. Curr Opin Neurobiol 22(3):383–388PubMedCrossRef
86.
Carlisle HJ, Kennedy MB (2005) Spine architecture and synaptic plasticity. Trends Neurosci 28(4):182–187PubMedCrossRef
87.
Grueter BA et al (2013) ∆ FosB differentially modulates nucleus accumbens direct and indirect pathway function. Proc Natl Acad Sci 110(5):1923–1928PubMedPubMedCentralCrossRef
88.
Robinson TE, Kolb B (2004) Structural plasticity associated with exposure to drugs of abuse. Neuropharmacology 47:33–46PubMedCrossRef
89.
90.
Kalivas PW (2009) The glutamate homeostasis hypothesis of addiction. Nat Rev Neurosci 10(8):561–572PubMedCrossRef
91.
92.
Robison A et al (2013) Behavioral and structural responses to chronic cocaine require a feed-forward loop involving? FosB and CaMKII in the nucleus accumbens shell. J Neurosci
93.
Russo SJ et al (2007) IRS2-Akt pathway in midbrain dopamine neurons regulates behavioral and cellular responses to opiates. Nat Neurosci 10(1):93–99PubMedCrossRef
94.
Graham DL et al (2007) Dynamic BDNF activity in nucleus accumbens with cocaine use increases self-administration and relapse. Nat Neurosci 10(8):1029–1037PubMedCrossRef
95.
Graham DL et al (2009) Tropomyosin-related kinase B in the mesolimbic dopamine system: region-specific effects on cocaine reward. Biol Psychiat 65(8):696–701PubMedCrossRef
96.
97.
Avidor-Reiss T et al (1996) Chronic opioid treatment induces adenylyl cyclase v superactivation involvement of Gβγ. J Biol Chem 271(35):21309–21315PubMedCrossRef
98.
Nestler EJ, Tallman JF (1988) Chronic morphine treatment increases cyclic AMP-dependent protein kinase activity in the rat locus coeruleus. Mol Pharmacol 33(2):127–132PubMed
99.
Terwilliger RZ et al (1991) A general role for adaptations in G-proteins and the cyclic AMP system in mediating the chronic actions of morphine and cocaine on neuronal function. Brain Res 548(1–2):100–110PubMedCrossRef
100.
Haghparast A et al (2014) Changes in the levels of p-ERK, p-CREB, and c-fos in rat mesocorticolimbic dopaminergic system after morphine-induced conditioned place preference: the role of acute and subchronic stress. Cell Mol Neurobiol 34(2):277–288PubMedCrossRef
101.
Morón JA et al (2010) Modulation of opiate-related signaling molecules in morphine-dependent conditioned behavior: conditioned place preference to morphine induces CREB phosphorylation. Neuropsychopharmacology 35(4):955–966PubMedCrossRef
102.
Chavez-Noriega LE, Stevens CF (1994) Increased transmitter release at excitatory synapses produced by direct activation of adenylate cyclase in rat hippocampal slices. J Neurosci 14(1):310–317PubMedPubMedCentralCrossRef
103.
Weisskopf MG et al (1994) Mediation of hippocampal mossy fiber long-term potentiation by cyclic AMP. Science 265(5180):1878–1882PubMedCrossRef
104.
Shaw-Lutchman TZ et al (2002) Regional and cellular mapping of cAMP response element-mediated transcription during naltrexone-precipitated morphine withdrawal. J Neurosci 22(9):3663–3672PubMedPubMedCentralCrossRef
105.
Cao J-L et al (2010) Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. Proc Natl Acad Sci 107(39):17011–17016PubMedPubMedCentralCrossRef
106.
Carlezon WA Jr, Duman RS, Nestler EJ (2005) The many faces of CREB. Trends Neurosci 28(8):436–445PubMedCrossRef
107.
Shaw-Lutchman TZ et al (2003) Regulation of CRE-mediated transcription in mouse brain by amphetamine. Synapse 48(1):10–17PubMedCrossRef
108.
109.
Barrot M et al (2002) CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli. Proc Natl Acad Sci 99(17):11435–11440PubMedPubMedCentralCrossRef
110.
DiNieri JA et al (2009) Altered sensitivity to rewarding and aversive drugs in mice with inducible disruption of cAMP response element-binding protein function within the nucleus accumbens. J Neurosci 29(6):1855–1859PubMedPubMedCentralCrossRef
111.
Larson EB et al (2011) Overexpression of CREB in the nucleus accumbens shell increases cocaine reinforcement in self-administering rats. J Neurosci 31(45):16447–16457PubMedPubMedCentralCrossRef
112.
113.
Li Y-Q et al (2008) Central amygdala extracellular signal-regulated kinase signaling pathway is critical to incubation of opiate craving. J Neurosci 28(49):13248–13257PubMedPubMedCentralCrossRef
114.
Baker DA et al (2003) Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse. Nat Neurosci 6(7):743–749PubMedCrossRef
115.
LaRowe SD et al (2007) Is cocaine desire reduced by N-acetylcysteine? Am J Psychiatry 164(7):1115–1117PubMedCrossRef
116.
117.
Solecki W et al (2009) Alterations of prodynorphin gene expression in the rat mesocorticolimbic system during heroin self-administration. Brain Res 1255:113–121PubMedCrossRef
118.
Maher CE, Martin TJ, Childers SR (2005) Mechanisms of mu opioid receptor/G-protein desensitization in brain by chronic heroin administration. Life Sci 77(10):1140–1154PubMedCrossRef
119.
Sim-Selley LJ et al (2000) Chronic heroin self-administration desensitizes μ opioid receptor-activated G-proteins in specific regions of rat brain. J Neurosci 20(12):4555–4562PubMedPubMedCentralCrossRef
120.
Sim LJ et al (1996) Effects of chronic morphine administration on mu opioid receptor-stimulated [35S] GTPgammaS autoradiography in rat brain. J Neurosci 16(8):2684–2692PubMedPubMedCentralCrossRef
121.
Kirschke C et al (2002) Effects of morphine withdrawal on μ-opioid receptor-stimulated guanylyl 5′-[γ-[35S] thio]-triphosphate autoradiography in rat brain. Eur J Pharmacol 446(1–3):43–51PubMedCrossRef
122.
Li S, Kirouac GJ (2008) Projections from the paraventricular nucleus of the thalamus to the forebrain, with special emphasis on the extended amygdala. J Comp Neurol 506(2):263–287PubMedCrossRef
123.
124.
Drdla R et al (2009) Induction of synaptic long-term potentiation after opioid withdrawal. Science 325(5937):207–210PubMedCrossRef
125.
Volkow ND, McLellan AT (2016) Opioid abuse in chronic pain—misconceptions and mitigation strategies. N Engl J Med 374(13):1253–1263PubMedCrossRef
126.
Vaccarino AL (1999) Tolerance to morphine analgesia: basic issues to consider. In: Pain Forum. Elsevier
127.
Rothstein JD et al (2005) β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature 433(7021):73–77PubMedCrossRef
128.
Bossert JM et al (2006) Activation of group II metabotropic glutamate receptors in the nucleus accumbens shell attenuates context-induced relapse to heroin seeking. Neuropsychopharmacology 31(10):2197–2209PubMedCrossRef
129.
Roberts-Wolfe DJ, Kalivas PW (2015) Glutamate transporter GLT-1 as a therapeutic target for substance use disorders. CNS Neurol Disord Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders) 14(6): 745–756
130.
Rogers J, Ghee S, See R (2008) The neural circuitry underlying reinstatement of heroin-seeking behavior in an animal model of relapse. Neuroscience 151(2):579–588PubMedCrossRef
131.
132.
Geoffroy H et al (2019) Morphine-Induced dendritic spine remodeling in rat nucleus accumbens is corticosterone dependent. Int J Neuropsychopharmacol 22(6):394–401PubMedPubMedCentralCrossRef
133.
Van Gucht D et al (2010) Smoking behavior in context: where and when do people smoke? J Behav Ther Exp Psychiatry 41(2):172–177PubMedCrossRef
134.
Lang PJ (2005) International affective picture system (IAPS): Affective ratings of pictures and instruction manual. Technical report
135.
Volkow N et al (2006) Las señales de la cocaína y la dopamina en el cuerpo estriado dorsal: mecanismo del deseo en la adicción a la cocaína. J Neurosci 26:6583–6588PubMedPubMedCentralCrossRef
136.
David SP et al (2005) Ventral striatum/nucleus accumbens activation to smoking-related pictorial cues in smokers and nonsmokers: a functional magnetic resonance imaging study. Biol Psychiatry 58(6):488–494PubMedPubMedCentralCrossRef
137.
Grüsser SM et al (2004) Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics. Psychopharmacology 175(3):296–302PubMedCrossRef
138.
Garavan H et al (2000) Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli. Am J Psychiatry 157(11):1789–1798PubMedCrossRef
139.
Poldrack RA (2006) Can cognitive processes be inferred from neuroimaging data? Trends Cogn Sci 10(2):59–63PubMedCrossRef
Metadata
Title
Addiction-induced plasticity in underlying neural circuits
Authors
Masoumeh Kourosh-Arami
Alireza Komaki
Masoumeh Gholami
Publication date
01-03-2022
Publisher
Springer International Publishing
Published in
Neurological Sciences / Issue 3/2022
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-021-05778-y

Other articles of this Issue 3/2022

Neurological Sciences 3/2022 Go to the issue

Original Article

Epidemiology, management and outcome of status epilepticus in adults: single-center Italian survey

COVID-19

Post-COVID-19 longitudinally extensive transverse myelitis: is it a new entity?

Original Article

New-onset status epilepticus in SARS-CoV-2 infection: a case series

Brief Communication

Paraneoplastic neurological syndromes associated with non-Hodgkin lymphoma: a case series

Original Article

Assessing mood and cognitive functioning in acute stroke: clinical usability of a Visual Analogue Mood Scale (VAMS)

Original Article

Early implementation of intended exercise improves quality of life in Parkinson’s disease patients