Study examines impulsiveness in Parkinson’s diseaseNov. 17, 2022, 9:32 AM
by Paul Govern
To manage symptoms of Parkinson’s disease, patients take drugs that modulate dopamine, a neurotransmitter with a major role in reward-motivated behavior.
Among the most common and debilitating side effects of these dopamine agonists, as the drugs are called, are so-called impulsive-compulsive behaviors, or ICBs, such as pathological gambling, hypersexuality and compulsive eating and buying.
The incidence of ICB in Parkinson’s has in various studies ranged from 14 to 40%.
As reported recently in Brain, neurologist Daniel Claassen, MD, MS, and colleagues used positron emission tomography, or PET, to assess aspects of dopamine release and its regulation in Parkinson’s patients with and without ICB.
Like other neurotransmitters, dopamine inhibits its own release, through so-called autoreceptors in the membranes of nerve cells.
And in the brain’s chief reward circuit, autoreceptors in the midbrain inhibit dopamine release farther down in an area called the striatum, where the ventral striatum regulates reward-related behaviors.
“As hypothesized, when we induced dopamine release in participants, those in our cohort with ICB had greater increases in the ventral striatum, a region that is particularly targeted by dopamine agonists,” said Claassen, professor of Neurology and chief of the Division of Behavioral and Cognitive Neurology. “We were able to connect this increase in dopamine to an impairment in midbrain autoreceptor proficiency in regulating this release.”
In the ventral striatum, alone among the study’s limbic, or emotion-related brain areas, the higher the participant’s ICB score, the greater the induced dopamine release.
“While our results reinforce what has become the established picture of dopamine regulation in the reward circuit, this is the first study to assess dopamine releases and link behavioral symptoms in a Parkinson disease cohort,” Claassen said.
Twenty early-to-mid-stage Parkinson’s patients, among them 10 with ICB, underwent dopamine agonist withdrawal and washout before completing two PET sessions over a two-week period. With participants blinded to the order of these sessions, in the first each participant was administered a placebo, while in the second each was administered an oral dose of amphetamine to stimulate endogenous dopamine release.
In both sessions, participants received a PET radiotracer, 18F-fallipride, which binds to unoccupied dopamine receptors, including autoreceptors. In the amphetamine state, with dopamine released to occupy its receptors, fewer binding sites are left available to the radiotracer.
With PET identifying the distribution of the radiotracer, Claassen was able to measure differences in dopamine release in the ventral striatum and other areas of interest.
The study’s first author is graduate student Alex Song. Others on the study include Kaitlyn Hay, Paula Trujillo, PhD, Megan Aumann, PhD, Adam Stark, Yan Yan, PhD, Hakmook Kang, PhD, Manus Donahue, PhD, and David Zald, PhD.
The study was supported by the National Institutes of Health (NS097783).