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Cerebral Cortex Advance Access published online on August 24, 2009

Cerebral Cortex, doi:10.1093/cercor/bhp179
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© The Author 2009. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Development of Cannabinoid 1 Receptor Protein and Messenger RNA in Monkey Dorsolateral Prefrontal Cortex

Stephen M. Eggan1, Yoshito Mizoguchi1, Samuel R. Stoyak2 and David A. Lewis1,2

1 Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA, 2 Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA

Address correspondence to Dr. Stephen M. Eggan, Department of Psychiatry, University of Pittsburgh, 3811 O’Hara Street, W1653 BST, Pittsburgh, PA 15213. Email: eggansm{at}upmc.edu.

Adolescent cannabis use is associated with an increased risk of schizophrenia and with impairments in cognitive processes reliant on the circuitry of the dorsolateral prefrontal cortex (DLPFC). Additionally, maternal cannabis use is associated with cognitive dysfunction in offspring. The effects of cannabis are mediated by the cannabinoid 1 receptor (CB1R), which is present in high density in the primate DLPFC. In order to determine how developmental changes in CB1Rs might render DLPFC circuitry vulnerable to cannabis exposure, we examined the density and innervation patterns of CB1R-immunoreactive (IR) axons and the expression of CB1R mRNA in the DLPFC from 81 macaque monkeys, ranging in age from embryonic 82 days to 18 years. Overall CB1R immunoreactivity in the gray matter robustly increased during the perinatal period and achieved adult levels by 1 week postnatal. However, laminar analyses revealed that CB1R-IR axon density significantly decreased with age in layers 1–2 but significantly increased in layer 4, especially during adolescence. In contrast, CB1R mRNA levels were highest 1 week postnatal, declined over the next 2 months, and then remained unchanged into adulthood. These findings provide a potential substrate for discrete, age-dependent effects of cannabis exposure on the maturation of primate DLPFC circuitry.

Key Words: cholecystokinin • GABA • interneurons • parvalbumin • schizophrenia


Stephen M. Eggan and Yoshito Mizoguchi have contributed equally to this work.


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