Tuesday, November 13, 2007

[125I]-LSD and [125I]-DOI label the claustrum

Three of the authors who found [125I]LSD and [125I]DOI binding in the rat choroid plexus also found a large quantity of radio-labeled drug in the claustrum (Yagaloff and Hartig, 1985; McKenna et al., 1989; Appel et al., 1990), a thin region of gray matter that is extensively connected with the insula and amygdala.

In the coronal slices of rat brain shown below, a white arrow points to a [125I]-DOI signal in rat claustrum, and two yellow arrows indicate [125I]-DOI in choroid plexus. In the third column, [3H]-ketanserin incubated with brain slices and [125I]-DOI prevented the specific binding of [125I]-DOI.



Terence McKenna said,
"Dennis used positron-emitting LSD. In fact, he actually solved the mystery of where does LSD go in the human brain. Ninety-five (95) percent of the labeled LSD ended up in the claustrum, which was completely a surprise. The claustrum is an ancient brain sub-organ way in the back, way underneath."
Terence may have been referring to his brother's work on the rat. Dennis McKenna used quantitative autoradiography to show that hallucinogens bind to rat claustrum.

The bar graph in the figure below shows the extent of [125I]-LSD and [125I]-R-DOI binding to frontal cortex, somatosensory cortex, claustrum, nucleus accumbens, and putamen of rats. The patterns of autoradiographic distribution of [125I]-LSD (white bars) and [125I]-R-DOI (hatched bars) were similar, but not identical (McKenna et al., 1989).




Neuroscientists have relied on lesion studies to study brain structures, but the claustrum cannot be easily ablated because it is very thin. The human claustrum has an average thickness of only 5 mm. Crick and Koch wrote:
"Given its extended and sheet-like topography, ablating or otherwise shutting this structure down in a controlled manner-without interfering with the fibres of passage or nearby regions-would require numerous, precisely targeted injections." (Crick,F.C. 2005)
PET and fMRI may be required to study the claustrum in the future. A high spatial resolution will be required to distinguish signal arising from the claustrum from the nearby caudate. Here is an illustration of the human claustrum and its curved shape in two coronal planes.


The claustrum makes reciprocal connections with the basal ganglia as well as most or all areas of the cerebral cortex, including the anterior cingulate cortex, precuneus, and dorsolateral prefrontal cortex. The connections of claustrum with thalamus appear to be mainly in the intralaminar and central nuclei. The function of the claustrum remains unknown.


Reference

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.

Crick F. C. and C. Koch (2005). What is the function of the claustrum? Philosophical transactions of the Royal Society of London. Series B, Biological sciences 360, 1271-1279. DOI:10.1098/rstb.2005.1661