Sunday, November 11, 2007

[125I]-LSD binds choroid plexus

Where does radio-labeled LSD bind?
"The rat choroid plexus accumulated the highest concentration of [3H]-LSD." (Diab,I.M. 1971)
Choroid plexus is in the brain, but choroid plexus cells are not typical neurons. In fact choroid plexus is epithelial tissue. Cells within the choroid plexus have the special function of synthesizing cerebrospinal fluid, CSF, which circulates the ventricles and spinal cord. Epithelial cells are less differentiated than neurons, so they are in a sense more primordial, and an unexpected target of [3H]-LSD binding.

In 1985, Yagaloff reported a high density of [125I]-LSD binding sites on the epithelial cells of the choroid plexus of adult rats. Figure 1 below is an autoradiogram of a coronal brain slice that was incubated with [125I]-LSD. The white arrows mark the choroid plexus.


The next figure is a closer view of the choroid plexus (CP). Within the ventricular (V) region, [125I]-LSD labeling was confined to the choroid plexus, not the walls of the ventricles.



In 1990, Appel and colleagues found that [125I]-DOI binds to choroid plexus dissected from male rats.


Appel reported that the choroid plexus, but not the walls of rat ventricle, are labeled by [125I]-LSD and [125I]-DOI.

In the figure below, "A" is an autoradiogram of a coronal brain slice that was incubated with [125I]-DOI. "B" is a brain slice that was incubated with [125I]-DOI and spiperone, a 5-HT2A receptor antagonist. In "B", [125I]-DOI is still bound to choroid plexus, indicating that [125I]-DOI may bind choroid plexus at sites other than 5-HT2A receptors, perhaps 5-HT1C receptors. "C" is a control.


McKenna incubated the radioligands [125I]-LSD, [125I]-R-DOI, and [125I]-S-DOI with slices of brain from adult male rats. He detected the highest binding density in the choroid plexus, ventricular areas, and claustrum.


Reference

Diab I. M., D. X. Freedman and L. J. Roth (1971). [3H]Lysergic acid diethylamide: Cellular autoradiographic localization in rat brain. Science 173, 1022-1024. DOI:10.1126/science.173.4001.1022

Yagaloff K. A. and P. R. Hartig (1985). 125I-lysergic acid diethylamide binds to a novel serotonergic site on rat choroid plexus epithelial cells. The Journal of Neuroscience 5, 3178-3183.

McKenna D. J., A. J. Nazarali, A. J. Hoffman, D. E. Nichols, C. A. Mathis and J. M. Saavedra (1989). Common receptors for hallucinogens in rat brain: A comparative autoradiographic study using [125I]LSD and [125I]DOI, a new psychotomimetic radioligand. Brain Research 476, 45-56. DOI:10.1016/0006-8993(89)91535-7

Appel N. M., W. M. Mitchell, R. K. Garlick, R. A. Glennon, M. Teitler and E. B. de Souza (1990). Autoradiographic characterization of (+-)-1-(2,5-dimethoxy-4-[125I] iodophenyl)-2-aminopropane ([125I]DOI) binding to 5-HT2 and 5-HT1c receptors in rat brain. The Journal of Pharmacology and Experimental Therapeutics 255, 843-857.