Year: 2014
Type: article
Abstract: Cocaine and amphetamine remodel dendritic spines within discrete cortico-limbic brain structures including the orbitofrontal cortex (oPFC). Whether dendrite structure is similarly affected, and whether pre-existing cellular characteristics influence behavioral vulnerabilities to drugs of abuse, remain unclear. Animal models provide an ideal venue to address these issues because neurobehavioral phenotypes can be defined both before, and following, drug exposure. We exposed mice to cocaine from postnatal days 31-35, corresponding to early adolescence, using a dosing protocol that causes impairments in an instrumental reversal task in adulthood. We then imaged and reconstructed excitatory neurons in deep-layer oPFC. Prior cocaine exposure shortened and simplified arbors, particularly in the basal region. Next, we imaged and reconstructed orbital neurons in a developmental-genetic model of cocaine vulnerability-the p190rhogap+/- mouse. p190RhoGAP is an actin cytoskeleton regulatory protein that stabilizes dendrites and dendritic spines, and p190rhogap+/- mice develop rapid and robust locomotor activation in response to cocaine. Despite this, oPFC dendritic arbors were intact in drug-naïve p190rhogap+/- mice. Together, these findings provide evidence that adolescent cocaine exposure has long-term effects on dendrite structure in the oPFC, and they suggest that cocaine-induced modifications in dendrite structure may contribute to the behavioral effects of cocaine more so than pre-existing structural abnormalities in this cell population.
Source: Frontiers in Pharmacology
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
Funders: Emory University, National Institutes of Health, Yerkes National Primate Research Center, Emory University, National Institute on Drug Abuse, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, Office of Research Infrastructure Programs, National Institutes of Health
OpenAlex ID: W2158858905