An imaginary fruit that makes its eaters forget their way home

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The Lotophagi (lotus eaters in Greek) were encountered by Odysseus and his sailors on an island in the troubled sea, shortly before facing the Cyclope (Homer, Odyssey IX 83-104). Whoever tasted the honey-sweet fruit of the flowering lotus, forgot the way home and desired to stay in lotus land. The fabulous lotus, never identified, is hence the ancient counterpart of modern "amnestic drugs. Actually, lotus was not the only potion renown in ancient times for its alleged amnestic powers. Drinking the water of the River Lethe (forgetfulness) in the Plain of Oblivion in Hades (the underworld, to which the souls travel) was supposed to erase all memory of earthly life (Plato, Republic 621).

A variety of real agents interfere with memory. Some are physical treatments, such as electric shock (Duncan 1948), including electroconvulsive therapy (ECT, Daniel and Crovitz 1983). In laboratory animals, a brief electric shock produces amnesia for a recently acquired task, provided that the treatment is administered during the first few hours after training. In humans, ECT induces a gradient of retrograde amnesia that may cover memories acquired up to 3 years before treatment (Squire et al. 1975). The effect of electric shock is construed as interference with "consolidation (Duncan 1948; McGaugh 1966; Squire et al. 1975).

Certain types of drugs produce amnestic effects as well. This could be due to their effect on arousal, on "attention, or on "acquisition, consolidation, or "retrieval of information. Drugs that impair recent memory when administered immediately after training, e.g. inhibitors of macromolecular synthesis or of "protein kinases, are highly useful in dissecting memory into "phases and in identifying the molecular and cellular mechanisms of short- and long-term "plasticity (Davis and Squire 1984; Montarolo et al. 1986; Rosenzweig et al. 1993). In general, if a drug enhances attention or "learning (Hock 1995; "nootropics), the antagonist has the opposite effect. Furthermore, the effects are dose dependent; some compounds that have beneficial effects on learning and memory have an opposite effect at higher concentrations. For example, caffeine at moderate doses is used to increase alertness and attention and hence creates favourable conditions for learning (Weiss and Laties 1962); but at high doses it impairs learning (Lashley 1917). The same is seen with other stimulants (e.g. Wetzel et al. 1981).

Perhaps most interesting for the general public is the amnestic effect of drugs widely prescribed in medical practice. 'Sedatives or hypnotics... taken in large doses retard the circulation. A clergyman was obliged to discontinue its use; he had very nearly lost his memory, which returned when the medicine was suspended' (Ribot 1882). Nowadays, anxiolytics of the benzodiazepine family (e.g. Valium) stand out as the most striking example. Benzodiazepines augment the efficacy of inhibitory neurotransmission by interacting with the

GABAa receptor complex in brain (Cooper et al. 1996). They are widely used as anxiolytics, hypnotics, muscle relaxants, and anticonvulsants. They also impair some cognitive abilities (Ghoneim and Mewaldt 1990; Izquierdo and Medina 1991; Danion et al. 1993; Gorenstein et al. 1995). Benzodiazepines are capable of interfering with long-term encoding of new episodic information without significantly affecting previously stored memory. They have little effect if at all on semantic memory or on non"declarative memory ("taxonomy). The amnestic effect is not correlated with the sedative and hypnotic effects of the drugs. Repeated administration results in some tolerance to the amnestic effect but does not abolish it (Ghoneim and Mewaldt 1990). Members of the benzodiazepine family have qualitatively similar effects on cognition, but in practice, some have more severe effects than others (ibid.). The most renown in terms of its amnestic effect is Flunitrazepam (Rohypnol). This drug has acquired the unflattering nickname of 'the rape drug' or 'date rape drug', because cases have been reported in which it was used as a prelude to sexual assault (Anglin et al. 1997). Flunitrazepam induces drowsiness and sleep, impairs motor function, and, most importantly, is remarkably amnestic. As the compound is water soluble, colourless, tasteless, and odourless, it can be slipped into a drink and afterwards, the victim may be unable to recall details of the assault. Owing to its abuse potential, flunitrazepam is now illegal in some countries.

With proper use, amnestic drugs do have a beneficial potential. They could be considered in severe shock and trauma. It is likely that in the years to come medicine will be equipped with an arsenal of specific memory erasers side by side with memory enhancers. In both cases, identification of specific steps in the encoding and the consolidation of new information (e.g. see "CREB, "immediate early genes) is expected to permit development of better memory targeted agents. Again, as is the case of other types of sophisticated technology, decisive regulations should be ensured to prevent abuse. In the meantime, benzodiazepines are already employed in anaesthesia and to calm unanaesthetized patients undergoing invasive and painful medical procedures. Forgetfulness of the unpleasant experience is in this case not an undesired side-effect but rather a blessing.

Selected associations: Amnesia, Attention, Fear conditioning, Nootropics

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