Autoradiographic study of pre- and postnatal distribution of cannabinoid receptors in human brain

Abstract

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.