Latent vulnerability in cognitive performance following chronic cocaine self-administration in rhesus monkeys

Porter, Jessica; Gurnsey, Kate; Jedema, Hank P.; Bradberry, Charles W.

doi:10.1007/s00213-012-2903-x

Cited by 13 publications

(11 citation statements)

References 48 publications

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“…This view is supported by observations that exposure of animals to drugs can produce cognitive and neural alterations that resemble those that are exhibited by substance-dependent humans (Jentsch et al, 2002; Nader et al, 2006; Porter et al, 2011; Groman et al, 2012; Porter et al, 2012). The coupling of neural changes following drug exposure with alterations in cognition (Groman et al, 2012) underscores the functional impact of such changes on behavior.…”

Section: Introductionmentioning

confidence: 83%

Methamphetamine-induced increases in putamen gray matter associate with inhibitory control

et al. 2013

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Rationale Problematic drug use is associated with difficulty in exerting self-control over behaviors, and this difficulty may be a consequence of atypical morphometric characteristics that are exhibited by drug-experienced individuals. The extent to which these structural abnormalities result from drug use or reflect neurobiological-risk factors that predate drug use, however, is unknown. Objectives To determine how methamphetamine affects corticostriatal structure and how drug-induced changes relate to alterations in inhibitory control. Methods Structural magnetic resonance images and positron emission tomography (PET) scans, assessing dopamine D2-like receptor and transporter availability, were acquired in monkeys trained to acquire, retain and reverse three-choice visual discrimination problems before and after exposure to an escalating dose regimen of methamphetamine (or saline, as a control). Voxel-based morphometry was used to compare changes in corticostriatal gray matter between methamphetamine and saline exposed monkeys. The change in gray matter before and after the dosing regimen was compared to the change in the behavioral performance and in dopaminergic markers measured with PET. Results Methamphetamine exposure, compared to saline, increased gray matter within the right putamen. These changes were positively correlated with changes in performance of methamphetamine-exposed monkeys in the reversal phase, and were negatively correlated with alterations in D2-like receptor and DAT availability. Conclusions The results provide the first evidence that exposure to a methamphetamine dosing regimen that resembles human use alters the structural integrity of the striatum and that gray-matter abnormalities detected in human methamphetamine users are due, at least in part, to the pharmacological effects of drug experience.

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Section: Introductionmentioning

confidence: 83%

Methamphetamine-induced increases in putamen gray matter associate with inhibitory control

et al. 2013

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“…It should also be pointed out that latent cognitive deficits not apparent under standard conditions can exist. For example, with these same monkeys, we previously demonstrated that reversal impairments that had normalized upon cessation of cocaine re-emerged when attentional distractors were added to the task (Porter et al 2013). …”

Section: Discussionmentioning

confidence: 96%

“…The cocaine group was drug-free for 20 months prior to the start this study. During that time, they participated in behavioral studies that have been reported (Porter et al 2013), but did not undergo any drug exposure other than ketamine for TB testing or other routine clinical procedures. The animals are a subset of those used for a previous study of cognitive deficits associated with chronic cocaine self-administration (Porter et al 2011).…”

Section: Methodsmentioning

confidence: 99%

Altered cerebellar and prefrontal cortex function in rhesus monkeys that previously self-administered cocaine

et al. 2014

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Rationale Differences in brain function in cocaine users can occur even when frank deficits are not apparent, indicating neuroadaptive consequences of use. Using monkeys to investigate altered metabolic activity following chronic cocaine self-administration allows an assessment of altered function due to cocaine use, without the confound of pre-existing differences or polysubstance use often present in clinical studies. Objectives To evaluate alterations in metabolic function during a working memory task in prefrontal cortex and the cerebellum following one year of chronic cocaine self-administration followed by a 20 month drug-free period. Methods [18F] Fluorodeoxyglucose PET imaging was used to evaluate changes in relative regional metabolic activity associated with a delayed match to sample working memory task. Chronic cocaine animals were compared to a control group, and region of interest analyses focused on the dorsolateral prefrontal cortex (DLPFC) and cerebellum. Results Despite no differences in task performance, in the cocaine group, the cerebellum showed greater metabolic activity during the working memory task (relative to the control task) compared to the control group. There was also a trend towards a significant difference between the groups in DLPFC activity (p=0.054), with the cocaine group exhibiting lower DLPFC metabolic activity during the delay task (relative to the control task) than the control group. Conclusion The results support clinical indications of increased cerebellar activity associated with chronic cocaine exposure. Consistent with evidence of functional interactions between cerebellum and prefrontal cortex, these changes may serve to compensate for potential impairments in functionality of DLPFC.

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“…Full details of the self-administration procedure for this cohort of monkeys have been published previously (Porter et al, 2013, 2011). Briefly, for 2 periods over a 5 year span (SA1: 12 months and SA2: 19 months separated by a 27 month period of abstinence), subjects in the cocaine group self-administered cocaine intravenously using an FR30 reinforcement schedule: up to 6 infusions 0.5 mg/kg/infusion each day 4 days/week (Tue-Fri) during SA1; the same schedule was used during the first part of SA2.…”

Section: Methodsmentioning

confidence: 99%

“…In the same monkeys self-administering cocaine from which we previously reported impairment of cognitive performance (Porter et al, 2013; Porter et al, 2011), we assessed if any disruptions in activity-based sleep efficiency were related to these cognitive impairments.…”

Section: Introductionmentioning

confidence: 99%

Altered activity-based sleep measures in rhesus monkeys following cocaine self-administration and abstinence

Cortes

Gomez

Ehnerd

et al. 2016

Drug and Alcohol Dependence

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Background Impairments in sleep and cognitive function have been observed in patients with substance abuse disorders and may be potential factors contributing to drug relapse. In addition, sleep disruption may itself contribute to cognitive deficits. In the present study we examined the impact of prolonged cocaine self-administration and abstinence on actigraphy-based measures of night-time activity in rhesus macaques as an inferential measure of sleep, and determined whether sleep-efficiency correlated with cognitive impairments in the same subjects on drug free days. Methods Actigraphy data was obtained from a group of rhesus macaques intravenously self-administering cocaine (n=6) and a control group (n=5). Periods were evaluated during which the mean cumulative doses of cocaine were 3.0+0.0 and 4.5+0.2 mg/kg/day for 4 days (Tuesday-Thursday) each week. Results Actigraphy-based sleep efficiency decreased during days of cocaine self-administration in a dose-dependent manner. Consistent with this observation, sleep became more fragmented. Activity-based sleep efficiency normalized during the weekend without cocaine prior to cognitive assessment on Monday. The magnitude of activity-based sleep disruption during self-administration did not correlate with the level of cognitive impairment on drug free days. With continued self-administration, the impact of cocaine on activity-based sleep efficiency declined indicating the development of tolerance. Conclusions Cocaine self-administration disrupted sleep efficiency in rhesus macaques as measured by actigraphy, but normalized quickly in the absence of cocaine. The cognitive impairment observed on drug free days was unlikely to be related to disruption of the nightly activity patterns on days of cocaine self-administration.

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Latent vulnerability in cognitive performance following chronic cocaine self-administration in rhesus monkeys

Cited by 13 publications

References 48 publications

Methamphetamine-induced increases in putamen gray matter associate with inhibitory control

Methamphetamine-induced increases in putamen gray matter associate with inhibitory control

Altered cerebellar and prefrontal cortex function in rhesus monkeys that previously self-administered cocaine

Altered activity-based sleep measures in rhesus monkeys following cocaine self-administration and abstinence

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