Northwestern investigators have discovered that dopamine signaling in the brain’s dorsomedial striatum promotes the development of compulsive behaviors in animal models, according to findings published in Current Biology. Talia Lerner, PhD, assistant professor of Neuroscience, was senior author of the study.
Corticostriatal circuits are neural circuits connecting the brain’s cerebral cortex to the striatum, a cluster of neurons within the basal ganglia that are responsible for controlling movement and reward-seeking behaviors. Prior research suggested these circuits control the expression of compulsive behaviors commonly observed in obsessive-compulsive disorder (OCD) and substance misuse disorders.
While corticostriatal circuits were thought be involved, the precise mechanisms that cause compulsive behaviors to emerge have remained unclear. Lerner and colleagues hypothesized that dopamine activity, which regulates the plasticity of corticostriatal circuits, played a crucial role in this process.
For the current study, the investigators studied dopamine activity in two regions of the brain’s striatum, the dorsomedial striatum and the dorsolateral striatum, which are involved in different types of reward learning: the dorsomedial striatum is involved with goal-oriented learning behaviors, while the dorsolateral stratum is involved with habitual behaviors.
Although it was previously thought that habit played a role in compulsion, to their surprise, the team found that dopamine signaling activity was actually upregulated in the mice’s dorsomedial striatum, where it predicted the development of compulsive reward seeking behavior.
“If compulsion looks like habit, we might have expected that the dorsolateral stratum would be more involved, but that wasn’t what we saw,” said Jillian Seiler, PhD, a postdoctoral fellow in the Lerner laboratory and first author of the study.
The investigators then utilized excitatory and inhibitory optogenetics — using light to change the activity of neurons — to manipulate the activity of dopamine neurons innervating the dorsomedial striatum. They found that stimulating dopamine signaling in the dorsomedial striatum increased compulsive reward seeking and inhibiting dopamine signaling in the dorsomedial striatum decreased compulsive reward seeking, confirming that the associations they had observed were causal.
The findings improve the understanding of the root causes behind compulsive behaviors, which may help providers better determine which management strategies will work best for individual patients, as well as improve the design of management strategies overall.
According to Lerner, the study also highlights an opportunity to further study individual variability with compulsive behaviors.
“We saw this wide span in how likely the mice were to naturally become compulsive. Neurobiological variability is an interesting thing to take advantage of to understand how psychiatric illnesses might result from being on the tail ends of distributions, and looking what circuits control that variability in animal models will be really important for understanding human variability,” Lerner said.
The study was supported by the National Institutes of Health K99/R00 Award R00MH109569, a NARSAD Young Investigator Award from the Brain & Behavior Research Foundation, and National Institutes of Health Diversity Supplement R00MH109569-04S1.
