Cocaine is a powerful and highly addictive drug that has wrecked countless lives since its isolation in the 19th Century. Addicts are left with powerful cravings for years after kicking the habit, but no one knows how the drug retains its hold. Barbara Sorg and her colleagues from Washington State University and the University of Calgary explain that cocaine profoundly affects regions of the brain associated with memory formation; could the addicts' drug-altered memories hold the key to their addiction? Sorg suspected that cocaine either produced an extremely powerful initial memory that was hard to eradicate, or the drug impaired the brain's ability to `extinguish'the addiction memory by learning new habits that mask the old. But memory formation in human brains is highly complex, so Sorg and her colleagues decided to investigate the effects of cocaine on learning and memory extinction by turning to a creature with a much simpler memory network: the snail Lymnaea stagnalis, which regulates its breathing patterns with a scaled down 3-neurone network().
Knowing that dopamine is a key neurotransmitter involved in memory formation, the team began by testing the effects of cocaine on dopamine uptake in the snail's brain, and found that even a dose as low as 0.1 mol l-1 of cocaine reduced the snail's dopamine uptake significantly. Having established the level of cocaine that affected dopamine uptake and possibly memory formation, the team needed to test the drug's effects on the snail's breathing behaviour.
Sorg explains that in well oxygenated water, Lymnaea breathes through its skin, but as the oxygen levels drop the mollusc extends its pneumostome (a breathing tube) above the surface to breathe air and supplement the water's dwindling oxygen supply. After exposing the snails to 0.1 mol l-1 of the drug for an hour a day over a 5 day period, the team monitored the snail's breathing patterns when transferred to de-oxygenated water. The molluscs used their pneumostomes more often than they had before cocaine exposure, possibly because the drug subtly changed their metabolism.
Knowing that the snail's behaviour changed a little after drug exposure,the team tested the drug's effects on the snail's ability to form memories. They taught the molluscs to keep their pneumostomes closed at low oxygen levels by gently tapping them on the breathing tube when they came up for air,and then checked the snails' memories a day later. Both the cocaine-treated and `clean' snails remembered to keep their pneumostomes closed. Cocaine hadn't altered the treated snails' ability to form a memory, so Sorg turned to her second hypothesis; had the addicted snails lost the ability to`extinguish' the trained memory (to keep their pneumostomes closed) with a new memory to keep it open?
The team retrained the molluscs, this time allowing them to breathe uninterrupted when they extended their breathing tubes. When the team once again tapped the `clean' snail's pneumostomes, the snails continued breathing through them. The extinction training had worked and masked the original training. But when they tested the cocaine-treated molluscs with a gentle tap,the molluscs instantly closed their pneumostomes. Instead of recalling their new training, they returned to their old habits. They'd failed to extinguish the memory.
Having found that cocaine strongly interferes with memory extinction, the team are keen to identify the `fundamental processes underlying extinction learning' says Sorg, and adds that this may `have important applications for treatment in cocaine addiction'.
