Brain Areas Implicated in Cocaine Relapse and Addiction

Cocaine abuse is a major public health issue, with estimations of as high as 1% of the US population over 12 as abusers. Addiction to cocaine, and most substances for that matter, results in physical modifications in your brain which are persistant, and detrimental to many mental fuctions like learning. During and following cocaine addiction, changes occur in a brain region called the nucleus accumbens (NAc), which is important in natural reward pathways. It is a key player in the reinforcement of drug-taking.

A recent brief communication in Nature Neuroscience (Martin et al. 2006) describes a facinating study which provides a neural explantion as to why learning and memory is abnormally disrupted in drug abusers, due to modifications in activity in the NAc region. (More below the fold...)

What this group found that was so different was this: there exists a difference in NAc activity between rats that can control their drug intake vs. those who receive it passively. The group compared four animal groups: rats which controlled their drug intake by pressing a lever, rats which received drug (via a catheter) passively, rats which received nothing (sham controls), and rats which could control their food intake. Following a 19-day training period where each group received either drug, food, or nothing, synaptic plasticity in each group was recorded in an attempt to measure LTD. (LTD refers to "long term depression" which is a form of neural activity which, like "long term potentiation," is necessary for types of learning and memory. More on that here.

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The results were surprising. The group which self-administered cocaine had a significant decrease in LTD in the NAc following a one-day abstinence. The groups which received no drug and the ones that received self-administered food had no change in NAc activity, which could be expected, but the group which received passive cocaine also had no significant change in LTD.

What this translates to is this: it was not the pharmacological properties of cocaine which triggered the change in LTD (or else it would have occured in passive cocaine animals too) but rather the control over cocaine administration made all the difference. This suggests that an important component of addition is the drug-seeking behavior, as well as making a "choice" at some level to administer. The authors speculated that it is this mechanism which contributes to the difficulty of avoiding relapse following drug abstinence, insofar that the drug-seeking behaviors are biologically reinforced at least as much as the physical addition itselt.

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I once did a summary of coke lit. and wrote a street-speak version for clients of our service that were trapped in its use. I remember (vaguely now) some intriquing experiments on mice that used an antagonist to anandamide, the endogenous brain juice that facilitates cannabis high.
It turned out that the mice whose anandamide receptors were blocked,(who had been primed to do work for cocaine rewards and formerly hadn't wanted to eat or drink - just shoot coke -) now began to refuse coke and refuse to respond to cues for it. And started to prefer food & H2O again.
It appeared to go some way to justifying the approach taken by traditional 12step fellowships of suggesting addicts to one drug abstain from all.
Clients used to invariably tell me, that pot wasn't addictive - and they could take it or leave it. I used to tell them, if that is true, then surely you might decide to abstain for a year to increase your chances of staying off (whatever they were addicted to). Almost invariably the ones that stayed off the smoko for a year, got clean. Very few of the rest, that we followed up, did.
Thanx for your site, Mindlesley

By mindlesley (not verified) on 22 Nov 2008 #permalink

Wow, Shelley, the new banner looks fabulous - what an excellent idea to characterize the temporal transition of the modern woman neuroscientist! And a new headshot to boot - very authoritative!

The issue of personal control in substance abuse is a very important issue; just as important as social setting and positive or negative reinforcement from the environment, completely independent of the drug itself. Gotta say that I learned a lot from the post - keep it up, welcome, and congratulations!

I've been wondering whether a stimulant like ritalin could increase the addictive potential of, well, behaviors with addictive potential.

For instance, would gambling be more addictive, or a gambler more likely to get hooked, if it were done while under the influence of ritalin or a similar stimulant.

I'm not sure if 'internet addiction' is considered to be a genuine condition, but if so I would think it would be especially likely in people on the legal stimulants.

By Jon Hendry (not verified) on 11 Jun 2006 #permalink