Autoradiographic Study of Pre- and Postnatal Distribution of Cannabinoid Receptors in Human Brain

Functional Imaging Center, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
NeuroImage (Impact Factor: 6.36). 01/2002; 14(6):1463-8. DOI: 10.1006/nimg.2001.0939
Source: PubMed


Cannabinoid receptors have been characterized and localized in the brain of several species, including human. The pre- and postnatal distribution of human brain CB1 receptors was investigated using quantitative autoradiography with [(3)H]CP55,940 as a ligand. Normal fetal brains (N = 8, gestational age 14-24 weeks)were obtained from voluntary abortions. Normal (drug and pathology free) adult human brains (N = 16, age 18-78) were obtained from the medical examiner's offices in New York City and Jaffa, Israel. Brains were stored frozen at -70 degrees C and sectioned (40 microm) at -15 degrees C. The radioligand (5 nM) was incubated with the sections for 3 h at room temperature. Washed and dried sections were exposed to tritium-sensitive film along with standards for 7-28 days and autoradiograms quantitated using NIH Image software. In the fetal human brain, low densities of THC-displaceable, region-specific binding could be observed as early as 14 weeks gestation. Receptor density increased slowly with gestational age but did not reach adult levels by the end of the second trimester (24 weeks gestation). In addition, the distribution pattern in the fetal brains was markedly different from the adult pattern. The most striking difference was the very low density of binding in the fetal caudate and putamen. In contrast, the globus pallidus pars medialis has almost-adult levels of cannabinoid receptors by 17-18 weeks gestation. The relatively low and regionally selective appearance of cannabinoid receptors in the fetal human brain may explain the relatively mild and selective nature of postnatal neurobehavioral deficits observed in infants exposed to cannabinoids in utero.

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    • "They can be found mainly on the nerve cells (neurons) in central nervous system (CNS). In the brain, the distribution of CB1 is particularly marked in the regions responsible for motor coordination and movement (for example, cerebellum, basal ganglia, striatum and substantia nigra), attention and complex cognitive functions, such as judgment (for example, cerebral cortex), learning, memory and emotions (for example, amygdala and hippocampus) (10, 11). In addition, CB1 receptors are present to a lesser extent in some organs and peripheral tissues, including endocrine glands, salivary glands, leukocytes, spleen, heart and part of the reproductive, urinary and gastrointestinal systems. "
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    • "The changes in receptor densities were explored by measuring the specific binding to CB 1 R's of [ 125 I]SD7015, a novel CB1 radioligand. The specific binding values of the radioligand in the frontal cortex were found in the range between 200 and 270 fM/g_tissue, similar to the range found with other radioligands such as [ 3 H]CP55,940 (Biegon and Kerman, 2001) as well as with [ 35 S]GTPcS assay (Mato et al., 2003). Our results suggest an increased CB 1 R density in prefrontal cortex in all neuropathological stages of AD as compared to controls. "
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    • "Cannabinoid receptors are densely located in frontal cortex (Eggan & Lewis 2006; Glass, Dragunow & Faull 1997; Herkenham et al. 1990). Further, the cannabinoid receptor system develops relatively late (Biegon & Kerman 2001), and receptor densities peak during adolescence among rats (Rodriguez de Fonseca et al. 1993), potentially increasing sensitivity to cannabinoid effects in adolescents. Although the neurobiological consequences of chronic cannabinoid exposure are still unclear, alterations of these developing receptor systems may underlie spatial working memory changes among adolescent marijuana users. "
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