Developmentally divergent effects of Rho-kinase inhibition on cocaine- and BDNF-induced behavioral plasticity
Open accessAbstract
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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Animal studies support clinical observations that biological changes during adolescence increase addiction vulnerability.
“Animal studies support clinical observations that biological changes during adolescence increase addiction vulnerability.”
From Impact of Sleep and Circadian Rhythms on Addiction Vulnerability in Adolescents (2018) · cites this paper as [17]
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References 26 · Cited by 20
- Authors
- DePoy, L. M., Noble, B., Allen, A. G., & Gourley, S. L.
- Affiliations
- Emory University (US)
- Corresponding author
- Gourley, Shannon L.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 243
- Pages
- 171-175
- ISSN
- 0166-4328 (ISSN-L)
- PMC
- PMC3619219
- OpenAlex
- W2010624905
- Cited by
- 20
- References
- 26
- Citations by year
- 2023: 2 · 2021: 1 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 2 · 2013: 1
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Emory University
- National Institutes of Health (ODP51OD11132, P51OD011132)
- Yerkes National Primate Research Center, Emory University
- National Institute of Neurological Disorders and Stroke (P30NS055077)
- National Center for Research Resources (P51RR165)
- Office of Research Infrastructure Programs, National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- Rho kinase inhibition, fasudil, dendritic spine remodeling, prefrontal cortex, adolescence, cocaine-induced locomotor activity, brain-derived neurotrophic factor, orbitofrontal cortex, reward seeking, addiction, behavioral plasticity
- MeSH terms
- Animals, Behavior, Animal, Cocaine, Female, Male, Mice, Inbred C57BL, Motor Activity, Neuronal Plasticity, Reward, Brain-Derived Neurotrophic Factor, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Mice, Biozzi, Protein Kinase Inhibitors, Mice, rho-Associated Kinases
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