Article

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

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Cerebral Cortex (Impact Factor: 8.67). 09/2009; 20(5):1164-74. DOI: 10.1093/cercor/bhp179
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ABSTRACT 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.

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    • "GABAergic neurons in the prefrontal cortex are rich in CB1 receptors which, when activated, result in a decrease in extracellular GABA release (28). It has been hypothesized that repeated exposure to cannabis during adolescence may alter the balance of GABAergic inhibitory inputs to pyramidal neurons in the prefrontal cortex that could lead to impaired cognitive function (29). Furthermore, CU leads to increased extracellular dopamine; probably through the activation of CB1 receptors on GABAergic interneurons, which in turn disinhibit dopaminergic neurons (30). "
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    Frontiers in Psychiatry 10/2013; 4:128. DOI:10.3389/fpsyt.2013.00128
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    • "The robust decrease in CB1R mRNA expression in layer II from early life to adulthood in our human cohort agrees with previous findings in primate [67] and suggests strong regulation of neurotransmission by CB1Rs early in life (Figure 8). It is tempting to speculate that this CB1R down-regulation results in a gradual reduction in CB1R-mediated suppression of inhibitory presynaptic neurotransmission. "
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    • "All remaining animals were unperfused and experimentally naı¨ve. Monkeys were assigned to age groups (Supplementary Table S3) that were established by previous studies (Hashimoto et al. 2009; Eggan et al. 2010). RNA was isolated from the frontal pole (PFC area 10) due to the availability of existing tissue. "
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