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A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
Brain mGlu5 Is Linked to Cognition and Cigarette Smoking but Does Not Differ From Control in Early Abstinence From
Megan N McClintick1,2, Robert M Kessler2, Mark A Mandelkern1,3
1Veterans Administration of Greater Los Angeles System, Los Angeles, California, USA.
Background:
The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance.
Methods:
Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested.
Results:
MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus.
Conclusion:
Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance.
Insights
Methamphetamine use disorder (MUD) patients show normal brain metabotropic glutamate receptor subtype 5 (mGlu5) levels. However, mGlu5 levels in certain brain regions correlate with verbal learning, suggesting mGlu5-targeting medications could aid cognitive recovery.
Area of Science:
- Neuroscience
- Psychiatry
- Radiochemistry
Background:
- Metabotropic glutamate receptor subtype 5 (mGlu5) is implicated in methamphetamine exposure and cognitive function.
- Individuals with methamphetamine use disorder (MUD) often experience cognitive deficits.
- This study investigates mGlu5 in MUD patients and its relationship with cognitive performance.
Purpose of the Study:
- To evaluate metabotropic glutamate receptor subtype 5 (mGlu5) availability in the brains of individuals with methamphetamine use disorder (MUD).
- To assess the association between mGlu5 levels and cognitive performance in MUD patients.
- To explore the potential of mGlu5-targeting medications for cognitive rehabilitation in MUD.
Main Methods:
- Positron emission tomography (PET) with the radiotracer [18F]FPEB was used to measure mGlu5 total volume of distribution (VT) in 14 abstinent MUD participants and 14 controls.
- Cognitive functions including verbal learning, spatial working memory, and executive function were assessed using standardized tests.
- Statistical analyses examined correlations between mGlu5 VT, methamphetamine use history, tobacco use, and cognitive test results.
Main Results:
- No significant differences in global or regional mGlu5 VT were observed between MUD participants and controls.
- Methamphetamine use history did not correlate with mGlu5 VT.
- A significant positive correlation was found between verbal learning performance and mGlu5 VT in the dorsolateral prefrontal cortex and superior frontal gyrus across all participants.
Conclusions:
- Abstinent MUD patients do not exhibit evidence of mGlu5 brain downregulation.
- The association between mGlu5 availability in specific prefrontal cortex regions and verbal learning suggests a potential therapeutic target.
- Targeting mGlu5 may offer a promising strategy to improve cognitive deficits in individuals with MUD.
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