Dopamine D2 Receptor Blocker Cures Cocaine Addiction In Rats

Professor Malcolm Horne of the University of Melbourne's Howard Florey Institute has found that a drug which blocks the D2 receptor on dopamine neurons eliminates cocaine cravings in rats previously addicted to cocaine.

The Howard Florey Institutes Prof Malcolm Horne and his team successfully cured cocaine addiction without withdrawal symptoms in rats - a discovery that could help develop drug addiction treatments for humans. Cocaine increases dopamine, the bodys own feel good drug produced by the brain. Repeated use causes tolerance for the drug so that withdrawal results in low levels of dopamine and continuous use is required to keep dopamine at normal levels, and even higher doses to get the high levels of initial use. Cocaine withdrawal is often accompanied by mental and physical symptoms. The Florey scientists cured cocaine addiction in rats by fooling their brain cells into thinking that there was a shortage of dopamine. As a result, their brain cells made more dopamine, which meant cocaine was not needed to increase dopamine levels and the addiction was cured.

Dopamine production and nerve cell endings capable of releasing dopamine were increased when the D2 receptor was blocked by the drug.

Dopamine is released by specialised nerve endings in the brain called terminals. The amount of dopamine is sensed by the D2 receptor, which regulates whether more or less dopamine needs to be released. Hornes team discovered that the number of terminals increase or decrease according to the levels of dopamine and found that when dopamine levels are high, the D2 receptor not only shuts down dopamine synthesis, it also reduces the number of terminals. When dopamine is low, it gives the signal to produce dopamine and make more terminals. Prof Hornes team gave a drug that blocks the D2 receptor to cocaine addicted rats and found that they could increase the number of terminals even while the animals had free access to cocaine. With time, the rats stopped seeking cocaine, and even when re-exposed to the drug some weeks later, did not relapse in the way that would be expected. The rats normal dopamine levels had increased, curing the addiction and removing withdrawal symptoms such as anxiety.

The news release excerpted above and various Australian media reports on this study do not provide a name for the antipsychotic medication used by Professor Horne's team. However, many antipsychotics bind to D2 receptors including risperidone and olanzipine. Some of those drugs bind at serotonin receptors and other sites as well. So without more details from Horne's lab we can not be certain that the effect he saw was really due to the D2 receptor blocking effect. Still, if it works on humans the mechanism of operation is of secondary concern.

The paper that will provide the details is not out yet but you can watch for it in the journal Neurobiology of Disease.

D2 receptor blockers can cause the pituitary to make too much prolactin with all sorts of undesirable side effects.

Symptoms of hyperprolactinaemia include amenorrhoea, galactorrhoea, infertility, loss of libido and erectile dysfunction. Resulting hypogonadism may cause osteoporosis.

My guess is that many of those effects come from prolonged use of a D2 receptor blocker drug. This may not be a problem for cocaine addicts since Horne's work showed that the antipsychotic drug he used did not have to be taken indefinitely. The D2 receptor was blocked by the antipsychotic drug he used, more dopamine was produced by the brain, compulsion to use cocaine dropped, and then administration of the antipsychotic was halted.

The ability to cure drug addictions would reduce crime, child abuse, birth defects from pregnant moms on drugs, brain damage, and a whole host of other problems. Therefore we all stand to gain enormously from the development of effective treatments for curing drug addiction.