Dataset Information

Long-Term Cocaine Self-administration Produces Structural Brain Changes That Correlate With Altered Cognition.

ABSTRACT:

Background

An enduring question from cross-sectional clinical studies is whether the structural and functional differences often observed between cocaine users and healthy control subjects result from a history of drug use or instead reflect preexisting differences. To assess causality from drug exposure, true predrug baseline imaging and neurocognitive assessments are needed.

Methods

We addressed this fundamental question of causality using longitudinal anatomical magnetic resonance imaging and neurocognitive assessments in rhesus macaques. Cognitive tasks employed were stimulus reversal learning as a measure of cognitive flexibility/inhibitory control and delayed match to sample as a measure of visual working memory. Time points examined were before and following 12 months of chronic cocaine (n = 8) or water (n = 6) self-administration. A magnetic resonance imaging-only time point was also obtained following 2 years of forced abstinence.

Results

We identified localized patterns of gray matter density (GMD) changes that were largely concordant with cross-sectional clinical studies. These included decreases in orbitofrontal cortex, insula, amygdala, and temporal cortex. There was also a prominent increase in GMD in the caudate putamen. GMD decreases were significantly correlated with cognitive impairments across individuals only in select cortical regions. Following abstinence, changes in GMD in some regions, including the orbitofrontal cortex, insula, and amygdala, were persistent and thus may play an important role in risk of relapse following extended abstinence.

Conclusions

Cocaine use is causal in producing regional changes in GMD, and those changes appear to drive cognitive impairments.

SUBMITTER: Jedema HP

PROVIDER: S-EPMC7855373 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Long-Term Cocaine Self-administration Produces Structural Brain Changes That Correlate With Altered Cognition.

Jedema Hank P HP Song Xiaowei X Aizenstein Howard J HJ Bonner Alexandra R AR Stein Elliot A EA Yang Yihong Y Bradberry Charles W CW

Biological psychiatry 20200818 4

<h4>Background</h4>An enduring question from cross-sectional clinical studies is whether the structural and functional differences often observed between cocaine users and healthy control subjects result from a history of drug use or instead reflect preexisting differences. To assess causality from drug exposure, true predrug baseline imaging and neurocognitive assessments are needed.<h4>Methods</h4>We addressed this fundamental question of causality using longitudinal anatomical magnetic resona ...[more]

PMID: 33012519

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Project description:Chronic cocaine use is associated with neurobiological and cognitive deficits that persist into abstinence, hindering success of behavioral treatment strategies and perhaps increasing likelihood of relapse. The effects of current cocaine use and abstinence on neurobiology and cognition are not well characterized.Adult male rhesus monkeys with an extensive cocaine self-administration history (? 5 years) and age-matched control animals (n = 4/group) performed cognitive tasks in morning sessions and self-administered cocaine or food in afternoon sessions. Positron emission tomography and [(18)F]-fluorodeoxyglucose were employed to assess cerebral metabolic rates of glucose utilization during cognitive testing.Cocaine-experienced monkeys required significantly more trials and committed more errors on reversal learning and multidimensional discriminations, compared with control animals. Cocaine-naive, but not cocaine-experienced, monkeys showed greater metabolic rates of glucose utilization during a multidimensional discrimination task in the caudate nucleus, hippocampus, anterior and posterior cingulate, and regions associated with attention, error detection, memory, and reward. Using a delayed match-to-sample task, there were no differences in baseline working memory performance between groups. High-dose cocaine self-administration disrupted delayed match-to-sample performance but tolerance developed. Acute abstinence from cocaine did not affect performance, but by day 30 of abstinence, accuracy increased significantly, while performance of cocaine-naive monkeys was unchanged.These data document direct effects of cocaine self-administration on cognition and neurobiological sequelae underlying cognitive deficits. Improvements in working memory can occur in abstinence, albeit across an extended period critical for treatment seekers, suggesting pharmacotherapies designed to enhance cognition may improve success of current behavioral modification strategies.

Dataset Information

Long-Term Cocaine Self-administration Produces Structural Brain Changes That Correlate With Altered Cognition.

Background

Methods

Results

Conclusions

Publications

Long-Term Cocaine Self-administration Produces Structural Brain Changes That Correlate With Altered Cognition.

Similar Datasets

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