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

作者：DePoy Lauren M; Noble Benjamin; Allen Amanda G; Gourley Shannon L^*

来源：Behavioural Brain Research, 2013, 243: 171-175.

DOI：10.1016/j.bbr.2013.01.004

• Orbitofrontal
• Fasudil
• Learning
• ROCK
• Dependence
• Sensitization

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.

• 出版日期2013-4-15