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Anhedonia: A Comprehensive Handbook Volume I pp 279–308Cite as

Anhedonia in Mouse Models of Methamphetamine-Induced Drug Seeking Behavior

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Abstract

Mood enhancement induced by drugs of abuse, such as methamphetamine, is often followed by a period during which the mood state is depressed. This state is termed drug-induced withdrawal dysphoria. Desire to avoid this dysphoric state during withdrawal motivates drug seeking behavior to alleviate withdrawal symptoms, even in anticipation of those symptoms (e.g. negative reinforcement), and maintains drug seeking behavior in addicted individuals. The state associated with methamphetamine (METH) withdrawal has been characterized as a depressive-like syndrome characterized by dysphoria, anhedonia, anxiety, akinesia, self-injurious behavior, social inhibition and suicidal ideation. A core manifestation of the depressive symptoms of this state is anhedonia, defined as a diminished interest in or pleasure from rewarding stimuli. In human drug abusers it is difficult to dissociate pre-existing depressive symptoms from drug withdrawal-induced symptoms or exacerbation of existing symptoms. This may be particularly true for anhedonia, which may lead individuals to seek out stimuli that more strongly activate reward systems. Medication for the treatment of dysphoric and anhedonic states will be important for addiction treatment in METH abusers. There are currently no effective treatments for METH abuse, or for METH-induced withdrawal dysphoria or anhedonia. We have recently developed a mouse model of anhedonia in which social isolation reduces responses to a reinforcing stimulus (e.g. anhedonia), a state that is reversed by a type of environmental enrichment (i.e. a running wheel). These observations suggest that alleviation of METH-induced withdrawal dysphoria in mice may be effectively achieved by altering environmental conditions. This chapter considers this model and compares it to other models of anhedonia and considers the role that anhedonia may play in the maintenance of drug-seeking behavior.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

AMPH:

Amphetamine

BDNF:

Brain-derived neurotrophic factor

CB1 receptor:

Cannabinoid receptor 1

CCI:

Chronic constriction injury

CMS:

Chronic mild stress

DAT:

Dopamine transporter

DISC1:

Disrupted-in-Schizophrenia-1

EAAT2:

Excitatory amino acid transporter 2

FH:

Fawn-Hooded

FSL:

Flinders sensitive line

GABA:

γ-aminobutyric acid

GLT-1:

Glial glutamate transporter 1

GluN1:

Glutamate receptor, ionotropic, N-methyl-d-aspartate ζ1 subunit

Grin1:

Same as GluN1

HPA:

Hypothalamic-pituitary-adrenal

ICSS:

Intracranial self-stimulation

LH:

Learned helplessness

METH:

Methamphetamine

NAc:

Nucleus accumbens

NET:

Norepinephrine transporter

NMDA:

N-methyl-d-aspartate

NR1:

Same as GluN1

SD:

Sprague-Dawley

SERT:

Serotonin transporter

VGLUT1:

Vesicular glutamate transporter 1

WKY:

Wistar-Kyoto

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Acknowledgments

This research was supported, in part, by Grant-in-Aids for Researchers, Hyogo College of Medicine (2012 to JK; 2013 to NK) and intramural funding from the National Institute on Drug Abuse, USA (GRU and FSH).

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Authors and Affiliations

  1. Department of Pharmacology, Hyogo College of Medicine, Nishinomiya, Japan

    Junichi Kitanaka Ph.D., Nobue Kitanaka & Motohiko Takemura

  2. Molecular Neurobiology Branch, National Institute on Drug Abuse-Intramural Research Program, Baltimore, Maryland, 21224, USA

    F. Scott Hall & George R. Uhl

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  1. Junichi Kitanaka Ph.D.
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Correspondence to Junichi Kitanaka Ph.D. .

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  1. Haifa & Sha'ar Menashe Mental Health Center, Israel Institute of Technology, Hadera, Israel

    Michael S. Ritsner

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Kitanaka, J., Kitanaka, N., Hall, F.S., Uhl, G.R., Takemura, M. (2014). Anhedonia in Mouse Models of Methamphetamine-Induced Drug Seeking Behavior. In: Ritsner, M. (eds) Anhedonia: A Comprehensive Handbook Volume I. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8591-4_12

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