Why do the brains of cocaine-users shrink faster than the brains of non-cocaine users?

Question

http://news.sciencemag.org/sciencenow/2012/04/cocaine-may-age-the-brain.html?rss=1

Cocaine-dependent individuals showed a significantly greater-than-normal age-related decline in gray matter in prefrontal and temporal regions compared with healthy controls. By contrast, parts of the striatum appeared resistant to age-related volume decline in the cocaine-using group. Enlarged striatal volume has frequently been reported in stimulant-dependent individuals,5, 6 possibly reflecting a marker of reduced dopamine neurotransmission in this dopamine-rich brain region where drugs like cocaine work. Decline in striatal dopamine receptor density has been associated with normal age-related cognitive decline.7 The relative absence of age-related changes in the striatum of cocaine-dependent people may thus reflect another feature of an abnormal brain ageing process.

Could it be related to possible neurotoxicity, or to the long-term effects of dopamine receptor downregulation? Could the effects also be generalizable to those who take dopamine-based ADD medications?

A link to the Letter to the Editor appeared in Molecular Psychiatry to which the ScienceNow article refers:
Cocaine dependence: a fast-track for brain ageing?

Answer 1

The mechanism of action of cocaine is dependent on pre-existing dopamine production and secretion. Normally, secreted dopamine is cleared from the synapse via the dopamine transporter (DAT) located on presynaptic dopaminergic terminals. Cocaine inhibits this reuptake of dopamine, increasing it's duration of action on post-synaptic dopamine receptors. Thus, cocaine's effect depends on neuronal dopamine production. Without intrinsic dopamine, cocaine would have no effect. This is actual not exactly true though because cocaine also inhibits serotonin and norepinepherine reuptake transporters as well but the same argument applies to those neurotransmitters as well.

The overall effect of cocaine on the nervous system is extremely complex as it prolongs the action of dopamine, serotonin and norepinephrine wherever those reuptake transporters are present. There is a particularly high density of DAT in the basal ganglia and nucleus accumbens. What these areas of the brain normally do is under intense study and debate. The accumbens may play a role in goal directed behavior and incentive salience, which is the attribution of value to various actions or objects in the environment. This is what naturally guides us to perform one action over another. The simplistic view is that cocaine "highjacks" this system such that cocaine itself acquires greater incentive salience than natural reinforcers such as food, sex, money etc.

Getting back to the original question regarding why cocaine causes brain atrophy. This appears to be a finding quoted from a paper by the original inquirer. It is not obvious to me what the mechanism of this atrophy would be. I suggest you look at the discussion section of the paper from which that abstract was quoted to see what the authors suggest. However, to my knowledge, such atrophy has not been widely discussed in the cocaine literature but I could be wrong.

For further information see Sulzer. 2011. How Addictive Drugs Disrupt Presynaptic Dopamine Neurotransmission.

Answer 2

Cocaine hits the brain with dopamine creating the desired high, which, the users seek. When used repeatedly, the brain begins to confuse it's own production with the user's introduction. Slowly, the brain begins to depend on the user's introduction and slows its own production to the point where it no longer produces it. This lack of production causes the part of the brain responsible for dopamine to shrink. It shrinks because it is tissue that is not being used and therefore doesn't get the proper blood flow to it and begins lose its health. Blood stimulation is lost, cell health is lost and size is thereby lost.

The brains of heavy cocaine users display little to no age-related brain shrinkage as compared to non-users because their brain has already shrunk to its limit. The shrink is due to lack of fresh blood stimulation. It is like a sponge that no longer is getting water and shrivels. After 2 days the sponge stops shrinking, it doesn't eventually shrink to a dust particle. It shrinks to its water-free size, the same way the cocaine user's brain shrinks to a blood-stimulation-free size. Age can't further shrink what's already maxed out in shrinkage.