How Addiction Shapes the Brain

Professor Barry Everitt introduced us to some of the mechanisms behind addiction, and how it affects brain chemistry.  Also working on the effect of addiction on the brain is Professor Julie Kauer, from Brown University.

Chris - Now, you've been studying some of the connections in the brain. Tell us what you found.

Julie - Well, let's see. Briefly, there's been a growing theory in the field of people who study cellular changes that occur during addiction. The changes that occur in the brain are somewhat akin to those that occur with learning and memory. Over the last ten years or so there's been a growing number of research papers looking at this problem and trying to see whether or not the changes that occur in parts of the brain involved in say, dopaminergic function as Barry was mentioning, may be similar to those that happen in parts of the brain involved in memory.

Chris - So the same way as you learn your maths homework, you also learn to take drugs. What's the reward then in doing your maths homework versus the reward you get for taking drugs because drugs, temporarily, can change your mood. That's the attraction to most people of using them. Whereas learning and memory: what's the reward?

Julie - It's a little more complicated that that. It's a more basic mechanism that is similar between the two processes. It's not simply a learning to be addicted to a drug because it's rewarding whereas you may not find maths as rewarding. Instead the changes that occur during learning are a strengthening of the synapses, which is the connection between two neurons. There's considerable evidence that during learning what happens is that the synapses, the connections between cells, become stronger in parts of the brain that serve memory. However, in the parts of the brain that subserve addiction, as Barry mentioned before, the reinforcement for natural rewarding stimuli and things that are important for survival; the strengthening of those synapses that occurs by drug abuse may have pathological effect on the system that actually directly taps in to long-lasting, maladaptive changes in that circuitry. It's not that the same circuits that you're learning with during your maths homework are altered during your use of cocaine but rather it's a different part of the brain in which maybe the changes in synaptic strength are not appropriate and are perhaps even beyond what should normally happen with rewarding stimuli.

Chris - When we learn something we have a connection between nerve cell A and nerve cell B and that connection can be strengthened or weakened and that's the learning experience. How are you proposing that addictive drugs can affect that process? What's going on?

Julie - We found two things. First of all there's considerable evidence the neurons released dopamine which seems to play a key role in early response to drugs. Those neurons can be controlled by excitatory input onto them or inhibitory inputs onto them. There's a lot of evidence that a single exposure to a drug of abuse (and this seems to be multiple drugs from ethanol/alcohol to cocaine) all produce a strengthening of the excitatory synapses which then would drive those dopamine neurons to fire more frequently and for long periods of time which may contribute to the early effects of drugs. The other way that you could increase the firing and activity of dopamine neurons would be to reduce inhibitory inputs onto them. What my lab found was that a normal process that seems to occur is potentiating of those inhibitory circuits. This may exist as a way to balance the potentiating of excitatory synapses in a normal, healthy brain. What we found, intriguingly, was that if an animal was given morphine and then we looked 24 hours later we found that the inhibitory potentiation was completely absent.

Chris - So does this mean that potentially, one exposure to one of these nasty agents could have life-long consequences?

Julie - I don't know the answer to that question and we're very interested in finding it out. Clearly the work that my lab's been interested in can only really speak for initial effects of drugs. Very clearly, in most cases a single exposure to one of these drugs does not produce addiction. However, it's possible that taking the drug even once sets the stage, in a way, for the vulnerability issue.

Chris - Just very briefly to finish off, Julie, given that you've found this new mechanism or you're uncovering this new way of thinking about how addiction occurs you've therefore got another way to think about how to break an addiction. Could we block this process and therefore treat people who have an addition to various drugs via a new way?

Julie - The work that we have carried out has pinpointed a single molecule in this dopaminergic brain region called guanylate cyclase. What may be true is that if we were to modulate this drug target at the same time that an addictive drug like morphine were delivered to a person that we might be able to ameliorate any addictive properties of the drug that would develop over time without affecting its analgesic effects. As morphine is given frequently in the hospital, all the time, this might be a useful process. We don't know whether targeting this molecule would be able to reverse addiction which is clearly a very persistent problem.

Chris - It still sounds like a very fertile area to look into.