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Publication : Developmentally divergent effects of Rho-kinase inhibition on cocaine- and BDNF-induced behavioral plasticity.

First Author  DePoy LM Year  2013
Journal  Behav Brain Res Volume  243
Pages  171-5 PubMed ID  23327740
Mgi Jnum  J:197156 Mgi Id  MGI:5490943
Doi  10.1016/j.bbr.2013.01.004 Citation  DePoy LM, et al. (2013) Developmentally divergent effects of Rho-kinase inhibition on cocaine- and BDNF-induced behavioral plasticity. Behav Brain Res 243:171-5
abstractText  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.
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