Regulation of drug-taking and -seeking behaviors by neuroadaptations in the mesolimbic dopamine system.
Previous studies have identified several neuroadaptations to chronic drug use, but relatively few have been functionally linked to addiction-related changes in drug-taking and -seeking behaviors. This article summarizes our past and present studies on the contribution of drug-induced neuroadaptations in the mesolimbic dopamine system to addiction-related changes in drug self-administration and the propensity for relapse in drug withdrawal. Our studies suggest that drug-induced up-regulation in cyclic AMP (cAMP)-protein kinase A (PKA) signaling in the nucleus accumbens (NAc) contributes to escalating drug intake and a propensity for relapse by differentially altering the sensitivity of D1 and D2 dopamine receptors that regulate drug-taking and -seeking behaviors. In addition, our studies suggest that drug-induced neuroplasticity at excitatory synapses in both the ventral tegmental area (VTA) and the NAc also facilitates drug-seeking behavior and the propensity for relapse. Finally, the role of both transient and enduring neuroadaptations in regulating drug-seeking behavior is discussed in view of different learning- and memory-based interactions.
Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9070, USA. david.self@utsouthwestern.edu
David W
DW
Self
D000222:Adaptation, Physiological / Q000187:drug effects*; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D008032:Limbic System / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000502:physiology; D009714:Nucleus Accumbens / Q000201:enzymology / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D019966:Substance-Related Disorders / Q000503:physiopathology*; D015854:Up-Regulation
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D004298:Dopamine