Prefrontal cortex plasticity mechanisms in drug seeking and relapse.
Development of pharmacotherapy to reduce relapse rates is one of the biggest challenges in drug addiction research. The enduring nature of relapse suggests that it is maintained by long-lasting molecular and cellular adaptations in the neuronal circuitry that mediates learning and processing of motivationally relevant stimuli. Studies employing the reinstatement model of drug relapse in rodents point to an important role of the medial prefrontal cortex (mPFC), with distinct contributions of the dorsal and ventral regions of the mPFC to drug-, stress- and cue-induced drug seeking. Whereas drug-induced neuroadaptations in the dorsal mPFC function to enhance excitatory output and drive expression of drug seeking, recent evidence suggests that plasticity in the ventral mPFC leads to reduced glutamatergic transmission in this region, thereby impairing response inhibition upon exposure to drug-conditioned stimuli. Treatments aimed at restoring drug-induced neuroadaptations in the mPFC may help to reduce cue-reactivity and relapse susceptibility.
Van den Oever
Michel C
MC
Dept Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands. michel.van.den.oever@cncr.vu.nl
Spijker
Sabine
S
Smit
August B
AB
De Vries
Taco J
TJ
D000818:Animals; D058999:Drug-Seeking Behavior / Q000502:physiology*; D006801:Humans; D013287:Illicit Drugs / Q000494:pharmacology*; D008959:Models, Neurological; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*; D012008:Recurrence; D019966:Substance-Related Disorders / Q000503:physiopathology* / Q000517:prevention & control*
D013287:Illicit Drugs