title: Brain-derived neurotrophic factor and addiction: Pathological versus therapeutic effects on drug seeking.
abstract: Many abused drugs lead to changes in endogenous brain-derived neurotrophic factor (BDNF) expression in neural circuits responsible for addictive behaviors. BDNF is a known molecular mediator of memory consolidation processes, evident at both behavioral and neurophysiological levels. Specific neural circuits are responsible for storing and executing drug-procuring motor programs, whereas other neural circuits are responsible for the active suppression of these "seeking" systems. These seeking-circuits are established as associations are formed between drug-associated cues and the conditioned responses they elicit. Such conditioned responses (e.g. drug seeking) can be diminished either through a passive weakening of seeking- circuits or an active suppression of those circuits through extinction. Extinction learning occurs when the association between cues and drug are violated, for example, by cue exposure without the drug present. Cue exposure therapy has been proposed as a therapeutic avenue for the treatment of addictions. Here we explore the role of BDNF in extinction circuits, compared to seeking-circuits that "incubate" over prolonged withdrawal periods. We begin by discussing the role of BDNF in extinction memory for fear and cocaine-seeking behaviors, where extinction circuits overlap in infralimbic prefrontal cortex (PFC). We highlight the ability of estrogen to promote BDNF-like effects in hippocampal-prefrontal circuits and consider the role of sex differences in extinction and incubation of drug-seeking behaviors. Finally, we examine how opiates and alcohol "break the mold" in terms of BDNF function in extinction circuits.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Barker
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA.
authors.forename: Jane R
authors.initials: JR
authors.lastname: Taylor
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, 1081 BT Amsterdam, The Netherlands; Department of Molecular and Cellular Neurobiology, Neuroscience Campus Amsterdam, Center for Neurogenomics and Cognitive Research, Faculty of Earth and Life Sciences, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: Taco J
authors.initials: TJ
authors.lastname: De Vries
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: petersjl.upr@gmail.com.
authors.forename: Jamie
authors.initials: J
authors.lastname: Peters
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D058999:Drug-Seeking Behavior / Q000502:physiology*; D006801:Humans; D019966:Substance-Related Disorders / Q000378:metabolism* / Q000628:therapy
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: Alcohol; Brain-derived neurotrophic factor; Cocaine; Extinction memory; Hippocampal–prefrontal systems; Opiates