Dopamine imbalance and its effect on compulsive behaviors 3


Obsessive-compulsive disorder (OCD) is characterized by anxiety from intrusive thoughts (obsessions), repetitive behaviors to reduce anxiety (compulsions), or both.  While OCD is a relatively rare disorder, affecting only 1.6% of the population (Kessler et al., 2005b) at some point in their life, roughly half of the cases are severe and may be linked to suicide attempts, substantial work disability, or substance dependence (Kessler et al., 2005a).  This blog post focuses on the compulsive behaviors associated with OCD and evidence for an influence of the dopaminergic reward system.  I will discuss a couple of studies relating dopamine to a variety of compulsive behaviors and the effect of rewards on these compulsions.  I will then relate these findings to OCD.

Dopamine is related to reward processing in the brain, and it is too often linked to only the receipt of rewards.  This misconception is easy to make.  Increases in dopamine levels may increase rewards, and diminished dopamine definitely leads to less rewards.  However, it is often missed that dopamine actually creates the anticipation for reward.  If there is greater anticipation for reward, then more rewards can be received.  Similarly, if no rewards are anticipated, then any rewards received are not processed.  This distinction between anticipation and receipt of rewards is key to understanding the influence of the dopaminergic pathways on compulsive behaviors.

An early study of the reward system looked at the effect of self-stimuRats!lation in rats.  Olds (1958) reported that when rats with electrodes implanted in the hypothalamus self-stimulated for 26 straight hours at a continuous rate of more than 2000 responses an hour, then slept, and then resumed self-stimulation at the same rate.  This self-stimulation by the rats is an example of how a compulsive behavior can be maintained beyond the point of any health benefits and to the point where it is detrimental.  Similar patterns of compulsive behavior in humans can be found in drug addiction as people transition from casual usage to compulsive, and deterrents have little to no effect on behavior.  Not surprisingly, the dopamine system is also implicated in drug addiction in humans (Wise, 2002).

Another more recent study also uses self-stimulation of the hypothalamus in rats.  When rats are provided with a continuous supply of a palatable high-fat diet, they eat for extended periods and become obese (Johnson & Kenny, 2010).  Measurements of brain stimulation reward  threshold in the hypothalamus significantly increased in the obese rats, indicating that more stimulation was necessary for them to gain reward.  Additionally, the obese rats exhibited a reduced striatal dopamine D2 receptor (D2R) density and were resistant to changes in dietary behavior when the high-fat food became less available.

I propose that the striatum has become hyposensitive to dopamine as a homeostatic response to continuous activation, creating a need to resist the high rate of influx of dopamine to the striatum.  When the striatum releases an abnormal amount of dopamine into the synaptic cleft – more than can be degraded – the synaptic cleft becomes flooded with dopamine.  Some of the dopamine is brought back into the presynaptic cell by reuptake, but some continues to activate the postsynaptic cell.  The abundance of dopamine may then trigger the cell to be less receptive to new dopamine via the D2R.

Since the presynaptic cell can remove dopamine by reuptake, if the dopamine transporter (DAT) responsible for this process is not effective, synaptic activation will persist.  Another study shows that a particular DAT genotype is associated with activation of the ventral striatum during periods of reward anticipation (Dreher et al., 2009).  Using fMRI they investigated the activation of the striatum and prefrontal cortex (PFC) during reward anticipation and receipt.  Greater activation of the striatum was seen in people with DAT1 9-repeat genotypes, suggesting that uptake by the DAT was inhibited and activation persisted.

It is important to note that Dreher et al. report that reward anticipation is most robustly found in activation of the ventral striatum and reward receipt activates parts of the PFC.  Between these two studies we can see that reward anticipation is focused in the ventral striatum and that this anticipation drives compulsive behaviors.  This is evidence that compulsive behaviors, whether overeating or substance abuse, is linked to an imbalance in the dopaminergic reward system.  It appears that activation of the striatum is creating an expectation for reward, driving the animal to seek the reward.  When the reward is found, it does not satiate the expectation, and continued seeking for that reward ensues.

Panksepp (1998) points out that this seeking behavior is distinctly different than the receipt of reward.  Activation of the dopamine system through electrical stimulation or pharmacology causes rats to exhibit increased arousal and excited sniffing behavior, characteristic of the rat seeking for food.  When an animal finds food, it does not get more excited.  Instead it relaxes and becomes less excited.  This is the receipt of the reward and correlates with reduced activation of the subcortcial dopamine system.  An animal who has the striatum continuously activated will persistently seek the reward, even though the anticipation and expectation cannot be met.  I expect a similar outcome if there is anticipation of reward and either no reward is available or the reward processing is insufficient to satisfy the expectation.  In all of these cases there is an imbalance in the reward anticipation and receipt leading to a compulsive behavior.

Compulsive behaviors related to OCD likely derive from a similar imbalance in the dopaminergic reward system.  Perhaps continuous activation of the ventral striatum creates an undirected expectation for reward.  The unfulfilled expectation causes an anxious feeling and an urge to satisfy the void.  As a result, learned rituals are practiced to generate this reward.  However, the reward is likely too little and the ritual needs to be repeated.  Ideally, it is not repeated to the point of physical exhaustion like the rats in the Olds experiment.

References

Dreher, J. C., Kohn, P., Kolachana, B., Weinberger, D. R., & Berman, K. F. (2009). Variation in dopamine genes influences responsivity of the human reward system. Proceedings of the National Academy of Sciences106(2), 617-622.

Johnson, P. M., & Kenny, P. J. (2010). Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nature neuroscience,13(5), 635-641.

Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005a). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of general psychiatry62(6), 593-602.

Kessler, R. C., Chiu, W. T., Demler, O., & Walters, E. E. (2005b). Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Archives of general psychiatry62(6), 617-627.

Olds, J. (1958). Self-stimulation of the brain its use to study local effects of hunger, sex, and drugs. Science127(3294), 315-324.

Panksepp, J. (1998). Affective neuroscience: The foundations of human and animal emotions. Oxford university press.

Wise, R. A. (2002). Brain reward circuitry: insights from unsensed incentives.Neuron36(2), 229-240.


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3 thoughts on “Dopamine imbalance and its effect on compulsive behaviors

  • Kate Dahlgren

    Really fantastic post Willie; it really got me thinking! I’m sure your next posts will cover it, but I would definitely be interested in reading more about why you think OCD is so strongly associated with the dopaminergic system (particularly an imbalance in the reward pathway/striatum). I might be opening a can of worms here, but it would also be interesting to discuss whether or not compulsions really are “rewarding”. The DSM 5 criteria for OCD is that compulsions are primarily driven by a response to an obsession and would be rewarding due to the fact that they can alleviate anxiety. I’m not an expert on the reward pathway, but do you think that kind of negative reinforcement would activate the same type of circuitry as a pleasurable stimulus?

  • Heather Urry

    Like that rat, I’ll press a lever for food too… But, seeing no levers nearby, instead I’ll just register my curiosity about something. 🙂 Specifically, I’m wondering if there’s evidence suggesting differences in dopamine system function in people with and without OCD. On the surface, the compulsive behaviors of OCD (e.g., checking, handwashing) seem different in quality than the kinds studied in the context of reward expectation (overeating, self-stimulation).

  • willie Post author

    Both of your comments point out that I did not provide good evidence that the OCD behaviors I’m looking at are linked to the dopaminergic/reward system. There are a few articles that make a loose association. My next post will look more at some structural analysis of the brain and differences in people with and without OCD. Hopefully, this will help in giving some evidence for the relation.
    Also, I do think the behaviors are rooted in reward seeking eventhough they are done in cases where anxiety is trying to be reduced. First, there is some evidence that the lack of reward when reward is anticipated can lead to frustration and then anxiety. Also, a topic that I will go into 2 posts from now is the reinforcement of positive behaviors that are used to relieve the anxiety. For example, hand washing is a positive behavior initially. And this behavior gets rewarded, reinforcing the behavior. When some other reward is being sought but not found, one will fallback on other rewards that are available. Anyways, I’ll go into this more, hopefully, in a few weeks.