This week's finds in the journal

Anders Sandberg (asa@nada.kth.se)
01 Apr 1999 20:49:59 +0200

OK, this week is going to be "psychopharmacology week". I have piles of cognition enhancing papers:

Low blood sugar isn't a problem
Yet another memory enhancer: pBC264
Yet another memory enhancer: water
Attention enhancers: AF102B and THA
Reducing distractability with ABT-418, ABT-089 and (-)-nicotine Smell enhancer: SKF 38393
Vitamin D3 makes you happy
A new take on Algernon

The effects of food deprivation and incentive motivation on blood glucose levels and cognitive function
Michael W. Green, Nicola A. Elliman and Peter J. Rogers Psychopharmacology, 134 88--94, 1997

OK, glucose can improve memory. But what happens when blood glucose drops, does performance drop too? In severe cases it is obvious, but are mild food deprivation like missing a meal relevant for us who want to optimize our abilities? The authors tested the combinations of food/food deprivation (a missed meal) and more or less incentive (by getting a reward for being among the three best) on a test battery for memory, attention, reaction speed, mood etc. It turned out that despite lower blood sugar levels in the participants who got no food, they did not perform worse on cognitive tests (they apparently moved slightly more slowly on a finger tapping test, which might be a more physical effects). Incentives on the other hand enhanced reaction time, but not memory. So the moral seems to be: keep the blood glucose levels up, but don't worry about them too much. And money isn't everything, it just improves reaction time.

Cognitive enhancing effects in young and old rats of pBC_{264}, a selective CCK_{B} receptor agonist
K. Taghzouti, I. Lena, F Dellu, B.P. Roques, V. Dauge and H. Simon Psychopharmacology 143: 141--149 1999

Cholecystokinin (CCK) is a signal substance that is used here and there in the central nervous system; it is relatively little explored, but is known to be involved in anxiety and possibly memory. It seems that different receptors may even have opposite effects. The authors did a freeform test of recognition memory for rats treated with pBC264 (which binds to the B receptor): they were given a simple maze to explore, and after 6 hours they were returned to it but now an extra passage had opened. The time they spent exploring the new passage was compared to control rats, who don't seem to remember that this is something new. Rats who were given pBC264 either immediately after the first episode or 30 minutes before returning to the maze explored it significantly more often (rats who got the drug before the first encounter with the maze did not remember better). This held both for young and old rats. It seems that the drug improves retrieval, but it could be a more complex effect. Overall, the CCK effects on memory are a bit unclear, but here is yet another group of potential cognition enhancer.

Water enhances memory performance
Andrew P. Rawlins, Isaac L.F Oscarsson and Olga Lintzer Psychopharmacology 144: 23-30 1999

It was almost to be expected, given that just about everything seems to enhance memory. The authors did a double-blind study on the effects of water on a wide range of psychological tests given to 412 medical students. The results suggest that water at least enhances short-term memory, memory retrieval and memory encoding for verbal material. It did not improve reaction time, mood or attention. This of course means a lot of studies have to be re-evaluated since the "control" groups given water or saline solutions were actually not control groups but also drugged. The authors suggest that the way water affects the brain is by affecting the balance of ions in the cells; by diluting them somewhat the dynamics of the neurons could change and this would among other things enhance memory. Weird.

Divided attention-enhancing effects of AF102B and THA in aging monkeys J.O O'Neill, I.J Fitten, D.W. Siembieda, K.C. Crawford, E. Halgren, A. Fisher, D. Refai Psychopharmacology 143: 123-130 1999

My favorite neuromodulator, acetylcholine, is not just involved in memory but also attention. Since there is a great deal of interest in cholinergic drugs to help dementia, the authors compared two drugs on old and young monkeys who were given a divided attention task. The first drug, AF102B imitates the effect of acetylcholine, while THA inhibits cholinestrase (and hence increase the level). It turned out that both drugs worked both in old and young monkeys (performance increase 34% (THA) and 43% (AF102B)) without any side effects. It was a fairly small study, so more research is needed, but cholinergic drugs look promising.

Central nicotinic receptor agonists ABT-418, ABT-089 and (-)-nicotine reduce distractibility in adult monkeys
Mark A. Prendergast, William J. Jackson, Alvin V. Terry Jr., Michael W. Decker, Stephen P. Arnetic and Jerry J. Buccafusco Psychopharmacology 136: 50--58 1998

Attention isn't just the ability to focus resources on something, it is also the ability to ignore distractions. Can this be enhanced? The authors tested three drugs on monkeys doing a standard short-term memory test (DMTS) who were distracted by flashing lights. It turned out that all three drugs helped, (-)-nicotine just a bit and the other two significantly (7.5-25% better performance). Further, on non-distracted trials the ABTs also increased performance. By the way, ABT-418 has earlier been shown to improve memory. Seems to be a nice combination, especially since at least ABT-418 has less side effects than nicotine.

SKF 38393 enhances odor detection performance Richard L. Doty, Cheng Li, Ritu Bagla, William Huang, Cheryl Pfeiffer and Gary M. Broscic
Psychopharmacology 136, 75--82 1998

After we have enhanced memory and attention maybe it is time for the senses. Dopamine seems to be involved in smell (which fits in with the essay in _The Man Who Mistook His Wife for a Hat_ by Oliver Sachs about the man who experienced smells in an almost doglike way - that man had taken a dopaminergic drug). This paper studies how a D1 dopamine agonist affects the ability to detect odors in rats. It turns out to enhance their ability to detect various odors, and that a D2 agonist decreases the effect. This is fun, since it implies that the two receptors have diametrally different effects. At the same time it is not clear how much is direct enhancement and how much is due to the stimulant effects, but it looks like a promising field to look into.

Vitamin D_3 enhances mood in healthy dubjects during winter Allen T.G. Lansdowne and Stephen C. Provost Psychopharmacology 135 319--323 1998

Mood changes over the seasons, and it has been suggested that beside melatonin effects vitamin D3 (which is produced in the skin when in sunlight) might be involved. A number of volunteers were given 400 IU, 800 IU or no D3 for 5 days in late winter in a double-blind study. The vitaminated people reported more positive and slightly lowered negative affect. Good to know for our Australian friends now when they get the axial tilt against them.

By the way, check out

http://www.unitedmedia.com/comics/robotman/archive/robotman990322.html
http://www.unitedmedia.com/comics/robotman/archive/robotman990323.html
http://www.unitedmedia.com/comics/robotman/archive/robotman990324.html
for Robotman's take on the problems cognition enhancement research.
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Anders Sandberg                                      Towards Ascension!
asa@nada.kth.se                            http://www.nada.kth.se/~asa/
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