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Posts Tagged ‘Pharmacology’

A canna...Image by Getty Images via Daylife Psychiatrists and families that cope with mental illness have long been aware of far reaching familial risk. Although the new genomics greatly accelerates the identification of specific risk alleles; the direct functional and mechanistic connections between these tiny bits of nucleic acid and large-scale changes in neural activity and behavior is more often a matter of hand waving than hard science. Monory et al., in their article, “Genetic Dissection of Behavioural and Autonomic Effects of d9-Tetrahydrocannabinol in Mice” (doi:10.1371/journal.pbio.0050269) provide an excellent example of how to relate the effects of a given gene (the CB1 receptor) to changes in behavior (getting stoned, to put it blunt-ly) by first beginning to determine what CB1 expressing cell-types are necessary. For example, ever-mellow GABA-ergic neurons are not involved in mediating the effects of cannabinoids whilst excitatory glutamatergic neurons mediate hypolocomotor effects. Similar analyses of specific (gene x circuit) interactions will build important bridges between genetics and psychiatry. Why do the mice get to have all the fun ?

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Lysergic acid diethylamideImage via Wikipedia Without a doubt, one of the low points of any marriage comes when you have to select a new paint colors. To avoid unnecessary strain, I usually just go along to get along, but Mother Nature allows no easy escape from this inevitable moment in our life cycle. After a third trip to the paint store, I found myself literally, up the wall, painting another test patch in a dark upper corner. Whilst brushing away, I was reminded of a lecture by V. S. Ramachandran who happened upon a colorblind subject who reported subtle differences in the colors of certain digits. In their article, “We also observed one case in which we believe cross activation enables a colorblind synesthete to see numbers tinged with hues he otherwise cannot perceive; charmingly, he refers to these as “Martian colors.” Although his retinal color receptors cannot process certain wavelengths, we suggest that his brain color area is working just fine and being cross-activated when he sees numbers.“Jay Gingrich and colleagues report (DOI) that the serotonin 2A receptors mediate the “synesthesia-like” effects of psychoactive hallucinogens such as LSD specifically via pertussis toxin-sensitive heterotrimeric G(i/o) proteins and src. Now, I’m a fan of genetic conflict hypotheses of all sorts, and perfectly willing to acknowledge that Mother Nature has stacked the deck against my Y-chromosome in many ways, but as my wife complained, yet again, that the new color was not, “the color in her head”, I began to wonder about natural mechanisms of synesthesia and the natural history of HTR2A and Mother Nature’s often dark sense of humor.

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