Format

Send to

Choose Destination
Behav Brain Res. 2013 Apr 15;243:171-5. doi: 10.1016/j.bbr.2013.01.004. Epub 2013 Jan 14.

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

Author information

1
Department of Pediatrics, Emory School of Medicine, Atlanta, GA, United States.

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.

PMID:
23327740
PMCID:
PMC3619219
DOI:
10.1016/j.bbr.2013.01.004
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center