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5 Changes in the Phosphorylation and Trafficking of Glutamate Receptors

5 Changes in the Phosphorylation and Trafficking of Glutamate Receptors

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Motivational Deficits in Parkinson’s Disease…


PD is still largely unexplored. So, improving our understanding of STN-DBS mechanisms, especially those concerning non-motor disorders, represents a challenge for

research in human behavior and appears essential to improve treatment.


Concluding Remarks

Recent experimental and clinical evidence clearly highlights a critical role of dopamine in apathy in PD. Whether apathy intrinsically results from the loss of dopamine in the nigrostriatal system or the progression of dopamine loss toward more

limbic areas, or from other variables associated with STN-DBS, remains a matter of

debate. However, in light of the recent data presented in this chapter, it may be proposed that different etiological factors all contribute to the development and occurrence of apathy, or of different forms of apathy, in PD. For instance, the dopaminergic

dysfunctions resulting from neurodegenerative mechanisms may act synergistically

with the DBS of STN regions associated with the nigrostriatal and the mesolimbic

system to induce or to aggravate apathy. Moreover, although the present chapter

focuses on the role of dopamine, it must be emphasized that the noradrenergic and

serotoninergic systems are also likely to be involved in the pathophysiology of

PD-related neuropsychiatric symptoms (e.g. Ballanger et al. 2012; Delaville et al.

2012; Politis et al. 2012; Temel et al. 2007). Some forms of apathy, non-responsive

to dopaminergic medication, have also been found to be associated with executive

dysfunction (Dujardin et al. 2009; Starkstein and Brockman 2011) or with atrophy

of specific basal ganglia or cortical structures (Carriere et al. 2010; Reijnders et al.

2010). Therefore, apathy, and related affective impairments, in PD can be considered a complex and multifactorial entity.

Acknowledgments This work was supported by the Institut National de la Santé et de la

Recherche Médicale, Fondation NeuroDis, Association France Parkinson, Ministère de la

Recherche et de la Technologie (MRT), Région Rhône-Alpes (ARC 2), Fondation de France,

Agence nationale de la recherche (ANR13 SAMA001401), and Grenoble Alpes University.

S.C., S.B. wrote the chapter with the help of the other authors C.C. and M.S.

Conflicts of Interest none.


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Chapter 17

The Circuitry Underlying the Reinstatement

of Cocaine Seeking: Modulation

by Deep Brain Stimulation

Leonardo A. Guercio and R. Christopher Pierce



Drug addiction is a major public health concern in the United States and worldwide.

It is estimated that the total costs of substance abuse, including productivity, health,

and crime-related costs, exceed $600 billion annually in the United States alone

(National Drug Intelligence Center, 2011). Cocaine is the third most commonly

abused illegal drug, after marijuana and prescription painkillers (SAMHSA 2012).

In 2011, nearly five million Americans over the age of 12 used cocaine. In addition,

there were 1.4 million regular cocaine users aged 12 and older, comprising 0.5 % of

the American population (SAMHSA 2012). One of the major problems facing

cocaine addicts is the discouragingly high rate of relapse, even after prolonged

abstinence (Carroll et al. 1994; O’Brien 1997). Despite many years of preclinical

and clinical research focused on understanding the underlying neurobiological and

neurochemical basis of addiction, there are no FDA-approved pharmacotherapeutic

interventions for the treatment of cocaine abuse and relapse.

Cocaine craving and relapse into cocaine-taking behavior in abstinent addicts

can be precipitated by three major factors: stress, environmental stimuli previously

associated with drug taking, or re-exposure to the drug itself (Wit and Stewart

1981; Jaffe et al. 1989; O’Brien et al. 1992; Sinha et al. 1999). In an effort to better

understand cocaine taking and relapse of cocaine-seeking behavior in laboratory

L.A. Guercio

Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania,

Philadelphia, PA 19104, USA

Department of Psychiatry, Center for Neurobiology and Behavior, Perelman School of

Medicine, University of Pennsylvania, 125 S. 31st Street, Philadelphia, PA 19104, USA

R.C. Pierce, Ph.D. (*)

Department of Psychiatry, Center for Neurobiology and Behavior, Perelman School of

Medicine, University of Pennsylvania, 125 S. 31st Street, Philadelphia, PA 19104, USA

e-mail: rcpierce@mail.med.upenn.edu

© Springer International Publishing Switzerland 2016

J.-J. Soghomonian (ed.), The Basal Ganglia, Innovations in Cognitive

Neuroscience, DOI 10.1007/978-3-319-42743-0_17


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