Abstract
Psychostimulant drugs have powerful reinforcing and hedonic properties and are frequently abused. Cessation of psychostimulant administration results in a withdrawal syndrome characterized by anhedonia (i.e., an inability to experience pleasure). In humans, psychostimulant withdrawal-induced anhedonia can be debilitating and has been hypothesized to play an important role in relapse to drug use. Hence, understanding the neural substrates involved in psychostimulant withdrawal-induced anhedonia is essential. In this review, we first summarize the theoretical perspectives of psychostimulant withdrawal-induced anhedonia. Experimental procedures and measures used to assess anhedonia in experimental animals are also discussed. The review then focuses on neural substrates hypothesized to play an important role in anhedonia experienced after termination of psychostimulant administration, such as with cocaine, amphetamine-like drugs, and nicotine. Both neural substrates that have been extensively investigated and some that need further evaluation with respect to psychostimulant withdrawal-induced anhedonia are reviewed. In the context of reviewing the various neurosubstrates of psychostimulant withdrawal, we also discuss pharmacological medications that have been used to treat psychostimulant withdrawal in humans. This literature review indicates that great progress has been made in understanding the neural substrates of anhedonia associated with psychostimulant withdrawal. These advances in our understanding of the neurobiology of anhedonia may also shed light on the neurobiology of nondrug-induced anhedonia, such as that seen as a core symptom of depression and a negative symptom of schizophrenia.
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Abbreviations
- 5-HT:
-
5-Hydroxytryptamine (serotonin)
- Ach:
-
Acetylcholine
- ACTH:
-
Adrenocorticotropic hormone
- AMPA:
-
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
- CRF:
-
Corticotropin-releasing factor
- DA:
-
Dopamine
- ICSS:
-
Intracranial self-stimulation
- MDD:
-
Major depressive disorder
- NAc:
-
Nucleus accumbens
- nAchR:
-
Nicotinic acetylcholine receptor
- NMDA:
-
N-methyl-D-aspartate
- NPY:
-
Neuropeptide Y
- VTA:
-
Ventral tegmental area
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Acknowledgments
This work was supported by NIH research grants U01 MH69062, R01 DA11946 and R01 DA232090, and research grant 15RT-0022 from the Tobacco-Related Disease Research Program of the State of California. The authors wish to thank Mr. Michael Arends for outstanding editorial assistance and Ms. Janet Hightower for graphics.
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D’Souza, M.S., Markou, A. (2010). Neural Substrates of Psychostimulant Withdrawal-Induced Anhedonia. In: Self, D., Staley Gottschalk, J. (eds) Behavioral Neuroscience of Drug Addiction. Current Topics in Behavioral Neurosciences, vol 3. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2009_20
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