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, lacking an axon and forbidding any explanation where LSD might affect the "firing patterns" of chroroid plexus cells. 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 studied adult rats, and he reported a high density of [125I]-LSD binding sites on the epithelial cells of the choroid plexus. Figure 1 below is an autoradiogram of a coronal brain slice that was incubated with [125I]-LSD. The white arrows mark the choroid plexus.

From choroid plexus and ventricles


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.

From choroid plexus and ventricles


In 1990, Appel and others found that [125I]-DOI binds to choroid plexus dissected from male rats. [3]

From choroid plexus and ventricles


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. There is clearly [125I]-DOI still bound to choroid plexus in "B", indicating that [125I]-DOI binds choroid plexus at sites other than 5-HT2A receptors, perhaps 5-HT1C receptors. "C" is a control.

From choroid plexus and ventricles


Dennis McKenna incubated 3 radioligands, [125I]-LSD, [125I]-R-DOI, and [125I]-S-DOI with slices of adult male rats. He detected the highest binding density in the choroid plexus, claustrum, and ventricular areas. [4]


References

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

2. Yagaloff, K. A. and P.R. Hartig 1985. 125I-lysergic acid diethylamide binds to a novel serotonergic site on rat choroid plexus epithelial cells. J. Neurosci. 5, 3178-3183.

3. 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. J. Pharmacol. Exp. Ther. 255, 843-857.

4. 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 Res. 476, 45-56. DOI:10.1016/0006-8993(89)91535-7