Phasic dopamine release in appetitive behaviors and drug addiction.
Although dopamine is implicated in the development of addiction, it is unclear how specific dopamine release patterns are involved with drug seeking. Addictive drugs increase tonic dopamine levels on the order of minutes, as well as phasic dopamine release events that occur on a subsecond time scale. Phasic dopamine release is associated with the initiation of goal-directed behaviors, and has been shown to promote drug seeking. Prior experience with addictive drugs modulates the synaptic and intrinsic properties of dopamine neurons, affects the pattern of dopamine neuron firing and release, and alters dopamine-dependent behaviors related to drug addiction. In this review, we synthesize the known drug-dependent changes to the dopamine system along with the established functions of phasic dopamine release in order to provide a framework for conceptualizing the role of phasic dopamine release in drug addiction. Because drug addiction is commonly thought to involve changes in brain circuits important for natural reinforcement, we first present the role of phasic dopamine release in appetitive and goal-directed behaviors in the context of contemporary theories regarding the function of dopamine. Next, we discuss the known drug-induced changes to dopamine neurons and phasic release in both in vitro and in vivo preparations. Finally, we offer a simple model that chronic drug experience increases the contrast, or 'signal to noise', of phasic dopamine release to basal dopamine levels in response to drug-related stimuli, which could result in aberrant associations between cues and reinforcers that contribute to the development of addiction.
Wanat
Matthew J
MJ
Department of Psychiatry and Behavioral Sciences and Department of Pharmacology, University of Washington, Seattle, WA 98195, USA. wanat@u.washington.edu
Willuhn
Ingo
I
Clark
Jeremy J
JJ
Phillips
Paul E M
PE
D000818:Animals; D001070:Appetitive Behavior / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003463:Cues; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D012008:Recurrence; D012054:Reinforcement, Psychology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D019966:Substance-Related Disorders / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology
D002492:Central Nervous System Depressants; D004298:Dopamine