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The Old learn better when theyŽre \"high\" - at least as Mice

Endogenous cannabinoids retard cerebral ageing

You canŽt teach an old dog new tricks! No exhaustive scientific explanation has been found for this traditional wisdom as yet. For nobody knows which molecular processes actually induce the decline in learning ability. Experimental scientists have been attempting to throw more light upon this field. Earlier experiments had already revealed that juvenile mice,  once rendered genetically resistant to hashish, became "crack" learners. But scientists at Bonn University have now made an astonishing discovery - that in later years these animals, when sensitised  to narcotics, paradoxically learn much more slowly than animals of the same species, and that their brains age more rapidly. These discoveries have now been published in the renowned economic journal "Proceedings of the National Academy of Sciences".

There has long been controversy regarding the effects of hashish on the learning ability of  the consumer. Interest here has centred on  the "cannabinoids", a group of intoxicating chemical substances found in hemp plants, but which can also be synthesised to imitate the bodyŽs endogenous "endocannabinoids". These endocannabinoids are important messenger substances for the transmission of signals between nerve cells, and numerous studies have revealed that cannabinoids can impair the ability to memorise. Hence the consumption of hashish is considered to be a true "learning killer".

In order to improve our understanding of the effects of hashish on learning and memory processes, researchers at Bonn have bred mice whose brains lack a receptor for cannabinoids. In the case of these "knock-out" mice, the genes which form the so-called CB1 receptors were specifically eliminated, thus negating any effects hashish or endogenous cannabinoids might have had on them. In laboratory experiments, the juvenile knock-out mice proved to be real "swots" which mostly achieved better test results than the "normal"  members of their species. This had hitherto led to the conclusion that the endogenous cannabinoid system had a "braking" influence on the ability to learn.

But it is a different matter when the swots grow older. Adult animals reveal clear symptoms of debility. This was determined by scientists from Bonn working in conjunction with colleagues from Pompeu Fabra University in Spain, who concentrated their research specifically on age-dependent learning. For this, they presented juvenile, adult and old knock-out mice with diverse tasks demanding co-ordination, the ability to memorise, and to adapt their patterns of behaviour. The juvenile knock-out mice did, indeed, exhibit the expected superiority in learning ability. But then came the surprise: their adult "colleagues" displayed greatly reduced ability in the learning tasks than their "normal" relatives of the same age. Their learning ability to learn lay only at the level of old mice of the wild type.

"Our results indicate that lack of the CB1 receptor leads  to accelerated  deterioration of the learning function", says Professor Zimmer. The group found a further indication in the animalsŽ brains: "Knock-out mice lose nerve cells in the  hippocampus significantly earlier than do mice of the wild type". Information from diverse sensory systems is collected in the  hippocampus, where it is subject to further processing and subsequent storage. Hence this is the central nodal point for the consolidation of the brainŽs memory material.

The neuroscientists in Bonn have realised that too little is still known of the endogenous cannabinoid systemŽs  mode of functioning. In the meanwhile, drugs are already in their final phase of clinical testing and will shortly be put on the market, which block the CB1 receptor. These could be employed, for instance, for treating obesity and nicotine dependence. There might be risks involved, says Professor Zimmer: "We must ensure that these drugs will not have any long-term side-effects".

Prof. Dr. Andreas Zimmer
Life & Brain Center
Universität Bonn
Telephone: 0228/688 5300
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