Some of the hard work of fighting addiction to heroin or cocaine is in learning not to use the drug. And if drug use inhibits the generation of new neurons that facilitate learning, the problem becomes a vicious circle. Now, research presented at this week’s annual meeting of the Society for Neuroscience in Washington DC shows that increasing the brain’s ability to generate new neurons decreases drug-seeking behaviours in rodents. The implication is that therapies that boost neurogenesis may one day help drug addicts on the long road to recovery.
In one study, a team from the University of Illinois Urbana-Champaign presented ongoing work tracking the effects of aerobic exercise on the ability of mice to disassociate the memory of a particular setting with cocaine.
Earlier this year, graduate student Martina Mustroph and her colleagues reported in the European Journal of Neuroscience that aerobic exercise, which is linked to neurogenesis, helped mice learn that a particular chamber of a cage was no longer associated with cocaine. The researchers first trained mice to associate an injection of cocaine with the textured floor of one chamber of a cage. Given a choice of chambers, the trained mice would then spend more time in the cocaine-associated one. Once cocaine was no longer given, mice who exercised after the drug training reduced their time in the textured chamber more quickly than did sedentary mice.
In a poster presentation this week, Mustroph and her colleagues described an experimental set up that will help them to better understand the mechanisms for this effect on learning and drug-use context. Former drug addicts can experience strong cravings for their former favourite poisons simply by revisiting places in which they once used drugs. The researchers’ work will allow them to tease out whether running helped the mice learn to not associate the environment with cocaine or if exercise interferes with long-term consolidation of the initial association.
A similar connection between neurogenesis and the reduction of drug-seeking behaviour was described by graduate student Richard Cleva, of Arizona State University in Tempe, and his colleagues at a subsequent session. In this work, the researchers trained rats to self-administer heroin. By pressing a lever, the rats gave themselves an intravenous dose of the drug with a light and audio tone cue accompanying each hit.
After five days of training, the rats were given daily oral doses of a neurogenesis-promoting drug called P7C3. The drug was given for seven days along with heroin. Then, both P7C3 and heroin administration stopped, even if the rats pressed the lever.
Cleva and his colleagues found that rats given P7C3 pressed the newly ineffective lever less often than other rats. For example, on ‘cold-turkey’ day one, the treated rats pressed the lever about 40 times over 3 hours. The other rats pressed it about 80 times over the same duration.
The treated rats also did not exhibit signs of rodent relapse: after nine days without heroin, the P7C3-treated rats did not increase their lever pushes in response to the light and tone that had once been associated with heroin. Untreated rats increased their lever pushing in response to the cue.
Neuroscientist Paul Frankland at the Hospital for Sick Children in Toronto, Canada, says that the two studies and their authors’ interpretations suggest similar conclusions: that increasing neurogenesis helps rodents disassociate environmental cues from drug-seeking behaviour.
If the rodent results apply to humans, they may suggest a new type of therapy for drug addicts, many of whom learned to associate certain people, places and things with drug use. Disassociating aspects of life that trigger the urge to use is one of many challenges in the recovery process.
“By using a proneurogenic compound, we may be able to not only restore depleted brain cells, but also help them recover from addiction,” says Cleva.
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