title: Developmentally divergent effects of Rho-kinase inhibition on cocaine- and BDNF-induced behavioral plasticity.
abstract: Prefrontal cortical dendritic spine remodeling during adolescence may open a window of vulnerability to pathological stimuli that impact long-term behavioral outcomes, but causal mechanisms remain unclear. We administered the Rho-kinase inhibitor HA-1077 during three adolescent periods in mice to destabilize dendritic spines. In adulthood, cocaine-induced locomotor activity was exaggerated. By contrast, when administered in adulthood, HA-1077 had no psychomotor consequences and normalized food-reinforced instrumental responding after orbitofrontal-selective knockdown of Brain-derived neurotrophic factor, a potential factor in addiction. Thus, early-life Rho-kinase inhibition confers cocaine vulnerability, but may actually protect against pathological reward-seeking - particularly in cases of diminished neurotrophic support - in adulthood.
authors: Department of Pediatrics, Emory School of Medicine, Atlanta, GA, United States.
authors: Lauren M
authors: LM
authors: DePoy
authors: Benjamin
authors: B
authors: Noble
authors: Amanda G
authors: AG
authors: Allen
authors: Shannon L
authors: SL
authors: Gourley
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D038602:Mice, Biozzi; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D012201:Reward; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; D003042:Cocaine; C049347:fasudil