Chronic methadone treatment and repeated withdrawal impair cognition and increase the expression of apoptosis-related proteins in mouse brain

Tramullas, Mónica; Martı́nez-Cué, Carmen; Hurlé, María A.

doi:10.1007/s00213-007-0751-x

Cited by 40 publications

(21 citation statements)

References 59 publications

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“…Animal experiments in mice have revealed that methadone treatment (2.5-10 mg/kg) once daily for three weeks with repeated withdrawals on Saturdays and Sundays has a negative impact on cognitive function, regardless of whether methadone is detectable in brain tissues (5). In addition, neural apoptotic damage caused by chronic methadone administration occurs in mouse brain white matter (6) and correlates with memory dysfunction and depression in former heroin users receiving MMT (7).…”

Section: Introductionmentioning

confidence: 99%

Longitudinal behavioral and fMRI‑based assessment of inhibitory control in heroin addicts on methadone maintenance treatment

Zhang

et al. 2018

Exp Ther Med

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Abstract. The objective of the present study was to determine whether methadone maintenance treatment (MMT) in heroin-dependent patients affects inhibitory control, whether any MMT-induced changes correlate with methadone dose and MMT duration, and whether these changes depend on the psychological characteristics of patients, such as depression, anxiety and impulsivity. Response inhibition in the GO/NO-GO test was combined with functional magnetic resonance imaging (fMRI) scanning data to examine whether MMT affects inhibitory control in 21 heroin-addicted patients who had already undergone at least three months of MMT. Patients were evaluated one year prior to and after the MMT period. Participants exhibited no difference in their GO/NO-GO reaction time and accuracy rate, or in their false alarm rate under NO-GO conditions. However, increased activation was detected in numerous brain regions in their 12-month fMRI scans, although these were not in the frontal-striatal loop. Increased fMRI activation in the left precentral gyrus and superior temporal gyrus were negatively correlated with the daily methadone dose and total methadone dose during the one-year study period. In conclusion, these results suggested that MMT over one year does not significantly change the behavioral indicators of inhibitory control function in heroin-dependent patients. The increase in activation leads to the hypothesis that MMT over one year may increase cognitive inhibitory control, which may be the result of the combined negative effect of methadone and the positive effect of functional recovery after withdrawal of heroin.

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Section: Introductionmentioning

confidence: 99%

Longitudinal behavioral and fMRI‑based assessment of inhibitory control in heroin addicts on methadone maintenance treatment

Zhang

et al. 2018

Exp Ther Med

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“…There is also some evidence for impaired cognitive function in methadone treatment from the mouse model. Tramullas et al (2007) ascertained impairment of cognitive abilities by chronic methadone in the Morris water maze.…”

Section: Introductionmentioning

confidence: 99%

Cognitive function in short- and long-term substitution treatment: Are there differences?

Soyka

Zingg

Koller

et al. 2010

The World Journal of Biological Psychiatry

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Cognitive impairment in drug-dependent patients receiving methadone maintenance treatment has been reported previously, although the literature is limited and results remain controversial. Long-term effects under stable methadone maintenance treatment (MMT) and the possibility of improvement in cognitive performance during long-term substitution treatment have rarely been investigated. We performed a comparative study investigating differences in cognitive functions under short- and long-term methadone treatment to test the hypothesis that patients perform better under long- than under short-term MMT. Seventy-seven patients were assessed cross-sectional either at least 30 days after the start of MMT (short-term group, n=35) or after at least 6 months of MMT (long-term group, n=42) with a comprehensive neuropsychological test battery on intelligence, learning and memory, attention and executive functions. Urine screenings were performed immediately before neuropsychological testing to check for concomitant drug use. Our findings may suggest, with all due caution, a slightly better performance of the long-term group in executive functions and visuo-construction. No group differences were found in attentional functions and learning and memory. More longitudinal research and studies controlling for the effects of dosage and duration of opioid addiction are necessary to examine whether cognitive ability may improve under long-term MMT.

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“…However, administration of β-endorphin facilitated retrieval of a shuttle avoidance task (Izquierdo 1980), and morphine had no effect on the retrieval of inhibitory avoidance (Castellano and McGaugh 1989). Furthermore, Tramullas et al (2007;2008) found impairments on a Morris water maze task after chronic intermittent administration of methadone, but facilitation on a passive avoidance task. Evidently, the effects of acute mu agonists on retrieval appear dependent on the dose and on the nature of the task.…”

Section: Pumps Inmentioning

confidence: 95%

The effects of acute and chronic steady state methadone on memory retrieval in rats

et al. 2012

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Chronic methadone treatment and repeated withdrawal impair cognition and increase the expression of apoptosis-related proteins in mouse brain

Abstract: Our data suggest that neural apoptotic damage could contribute to impairment of the cognitive abilities of mice observed after chronic methadone administration and withdrawal.

Cited by 40 publications

References 59 publications

Longitudinal behavioral and fMRI‑based assessment of inhibitory control in heroin addicts on methadone maintenance treatment

Longitudinal behavioral and fMRI‑based assessment of inhibitory control in heroin addicts on methadone maintenance treatment

Cognitive function in short- and long-term substitution treatment: Are there differences?

The effects of acute and chronic steady state methadone on memory retrieval in rats

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