A BDNF infusion into the medial prefrontal cortex suppresses cocaine seeking in rats.
The medial prefrontal cortex (mPFC) is critical for reinstatement of cocaine seeking and is the main source of brain-derived neurotrophic factor (BDNF) to striatal regions of the brain relapse circuitry. To test the hypothesis that BDNF in the mPFC regulates cocaine-seeking behavior, rats were trained to press a lever for cocaine infusions (0.2 mg/inf, 2 h/day) paired with light+tone conditioned stimulus (CS) presentations on 10 consecutive days. After the last self-administration session, rats received a single infusion of BDNF (0.75 microg/0.5 microL/side) into the mPFC; this manipulation produced protracted effects on cocaine-seeking behavior (non-reinforced lever pressing). BDNF pretreatment administered after the last session attenuated cocaine seeking 22 h later and, remarkably, it also blocked cocaine-induced suppression of phospho-extracellular-regulated kinase and elevated BDNF immunoreactivity in the nucleus accumbens. The same pretreatment also suppressed cocaine-seeking behavior elicited by response-contingent CS presentations after 6 days of forced abstinence or extinction training, as well as a cocaine challenge injection (10 mg/kg, i.p.) after extinction training. However, BDNF infused into the mPFC had no effect on food-seeking behavior. Furthermore, BDNF infused on the sixth day of abstinence failed to alter responding, suggesting that the regulatory influence of BDNF is time limited. The suppressive effects of BDNF infused into the mPFC on cocaine seeking indicate that BDNF regulates cortical pathways implicated in relapse to drug seeking and that corticostriatal BDNF adaptations during early abstinence diminish compulsive drug seeking.
Berglind
William J
WJ
Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
See
Ronald E
RE
Fuchs
Rita A
RA
Ghee
Shannon M
SM
Whitfield
Timothy W
TW
Miller
Scott W
SW
McGinty
Jacqueline F
JF
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects; D004333:Drug Administration Routes; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055502:Secondary Prevention; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D018765:Dopamine Uptake Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D003042:Cocaine