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.