I have heard a lot of folks with early onset Parkinson’s talk about how a dopamine agonist made them behave compulsively: excessive gambling, hypersexuality, incessant computer use, shopping. Although the research still needs to be done, my background in neuroscience and the psychology of learning allows me to propose a hypothesis for what might be going on.
According to learning theory, when a behavior is reinforced, it will tend to occur more often. The treat you give your dog after she sits on your command reinforces sitting behavior by making it more likely to happen the next time you give your command. The dog associates the “sit” command with the pleasure of the treat and will learn to respond to the command with the target behavior. With proper reinforcement you can teach any dog new tricks.
However, all this learning has to correspond with some type of activity in the brain. This is where dopamine comes into play. During this learning process, small amounts of dopamine activate nerve tracts associated with reinforcement. These tracts form a complex loop between higher order structures in the brain, including elements of the basal ganglia, a portion of the brain very familiar to people who have Parkinson’s. The dopamine inputs activate reward and pleasure centers that evaluate how interesting the triggering event has been. If it is sufficiently interesting, the event is encoded as a memory available for future reference.
When reward circuits are stimulated, pleasurable activities can feel more reinforcing. I have found that many, if not most, of the problematic activities patients report occurring because of dopamine agonists were things a person already enjoyed. Previously, however, the enjoyment was not compulsive. I believe that when a reward circuit is chronically activated in conjunction with an activity already perceived to be pleasurable, it can cause the behavior to occur more frequently. Increased behavior results in increased opportunity for it to become reinforced. We would call this compulsivity.
I have oversimplified a very complex process. However, it is one I learned a great deal about when I worked with individuals who abused methamphetamines (“meth”) at inpatient treatment facility. Methamphetamine increases the amount of dopamine available at the synapses so that more is available for receptors on the other side of the junction. The net effect is to stimulate dopamine circuits, including the ones involved in evaluating reward potential. There are many stories of chronic methamphetamine users engaging in seemingly meaningless repetitive behaviors like sorting things, drawing intricate pictures, disassembling and rebuilding mechanical things. This obsessive-compulsive “tweaking” or “punding” behavior is very well known among users and treatment professionals. There are also well-documented cases of chronic users engaging in compulsive sex and computer use.
The behaviors we saw in chronic methamphetamine patients are precisely the kind reported with PD dopamine agonists, albeit much less severe. This is because real dopamine released by the action of methamphetamines fully stimulates the receptors, whereas dopamine agonists do so only partially. There are also several different types of dopamine receptors and the dopamine agonists were originally thought to be relatively unattractive to the receptors linked with reward. This is probably the case for most but not all who take these medications for PD. For reasons that still aren’t clear, whereas some people do find that the agonists can enhance reward potential, most people are not affected.
At this time, it is very difficult to predict who might be particularly sensitive to enhanced reinforcement from dopamine agonists. It is however, very important for everyone to be vigilant about the possibility that problems with compulsive behavior could arise. In my next blog, I will discuss some of the warning signs that dopamine agonists might be causing compulsive behaviors.