Chronic methamphetamine self-administration disrupts cortical control of cognition

doi:10.1016/j.neubiorev.2016.07.020

Neuroscience & Biobehavioral Reviews

Volume 69, October 2016, Pages 36-48

https://doi.org/10.1016/j.neubiorev.2016.07.020 Get rights and content

Highlights

•
Human methamphetamine abusers exhibit cognitive deficits to varying degrees.
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Extended meth access in rats impairs attentional processing and recognition memory.
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These deficits result from cortical alterations following extended meth access.
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Other cognitive dimensions and related structures are largely unexplored.
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Medication restoring these deficits may help to maintain abstinence in meth addicts.

Abstract

Methamphetamine (meth) is one of the most abused substances worldwide. Chronic use has been associated with repeated relapse episodes that may be exacerbated by cognitive impairments during drug abstinence. Growing evidence demonstrates that meth compromises prefrontal cortex activity, resulting in persisting attentional and memory impairments. After summarizing recent studies of meth-induced cognitive dysfunction using a translationally relevant model of self-administered meth, this review emphasizes the cortical brain changes contributing to cognitive dysregulation during abstinence. Finally, we propose the use of cognitive enhancers during abstinence that may promote a drug-free state by reversing cortical dysfunction linked with prolonged meth abuse.

Section snippets

Background

Methamphetamine addiction, as any addiction with other abused substances, is a chronic relapsing disorder meriting the need for effective treatment strategies. The development of such strategies relies on concerted efforts by researchers to integrate findings from basic animal scientists and human clinical scientists with those of practitioners conducting clinical trials. Despite gains in our knowledge of meth, the effects of repeated meth abuse, and the severity of this problem, no treatments

Models of meth administration used to study cognitive dysfunction

Although there is a presumed relationship between drug-seeking, cognitive deficits, and neural dysfunction, it is difficult to establish whether these deficits are caused by meth or a cognitive predisposition, since human subjects undergo evaluation well after they have become addicted. A major strength of preclinical research is the ability to study these relationships in a controlled manner using translationally relevant animal models.

Experimenter-administered meth, consisting primarily of

Attention, inhibitory control, and cognitive flexibility

The ability to adapt behavior according to current environmental or situational demands requires cognitive control by attending to task relevant information over extended periods of time, regardless of attentional interference (Botvinick et al., 2001). These dimensions are particularly relevant to dissociate recreational from compulsive drug intake in addiction. For instance, deficits in response inhibition could account for the inability of a subject to resist the urge of drug taking when

Recognition memory

In humans, episodic memory is a form of declarative memory that implies the use of previously acquired autobiographic information for conscious recall (Tulving, 2002). Meth impacts this particular type of memory (Scott et al., 2007), and this impairment has been proposed to contribute to relapse in meth addicts (Simon et al., 2004). For example, addicts that had just relapsed for meth had higher deficits in episodic memory than abstinent meth addicts, and also when compared to individuals who

Chronic meth SA neurotoxicity in subcortical areas

The cognitive impairments reviewed above focused on cortical dysfunction. However, extended meth access could also affect subcortical areas to induce cognitive sequelae. Standard markers of neurotoxicity after meth include marked reduction of dopamine and serotonin levels, reduction in striatal monoamine transporters, and gliosis. As reviewed by Krasnova and colleagues, repeated meth injections result in consistent signs of neurotoxicity in subcortical regions (Krasnova and Cadet, 2009). In

Medications that reduce cognitive deficits without abuse potential

Some cognitive and neuronal deficits induced by meth appear to recover with time (Salo et al., 2009, Volkow et al., 2001b). However, in the interim, cognitive dysfunction may distract users from treatment compliance as addicts often report continued use of meth to “make them feel normal” (Bungay et al., 2006). Unfortunately, other cognitive impairments seem to persist even after protracted period of abstinence. Besides displaying even more cognitive impairments than opiate abusers, meth addicts

Concluding remarks

The studies reviewed here highlight some of the key cognitive domains as a result of extended access to methamphetamine self-administration. The impairments in attentional processing (5-choice serial reaction time task), cognitive set-shifting, and object recognition memory pinpoint a particular vulnerability in cortical areas to meth-induced dysregulation (Fig. 4). The use of contingent models of meth self-administration show that long access, but not short access to meth, is more likely to

Acknowledgement

Support for this review was from NIH/NIDA grant R01DA033049.

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Review articleChronic methamphetamine self-administration disrupts cortical control of cognition

Highlights

Abstract

Section snippets

Background

Models of meth administration used to study cognitive dysfunction

Attention, inhibitory control, and cognitive flexibility

Recognition memory

Chronic meth SA neurotoxicity in subcortical areas

Medications that reduce cognitive deficits without abuse potential

Concluding remarks

Acknowledgement

Neuropsychopharmacology

Neuropharmacology

Behav. Process.

Behav. Brain Res.

Pharmacol. Biochem. Behav.

Trends Neurosci.

Neuropsychologia

Neurobiol. Learn. Mem.

Neuropsychopharmacology

Behav. Brain Res.

Pharmacol. Biochem. Behav.

Neurosci. Biobehav. Rev.

Pharmacol. Biochem. Behav.

Neuron

Pharmacol. Biochem. Behav.

Behav. Brain Res.

Behav. Brain Res.

Biol. Psychiatry

Behav. Brain Res.

Brain Res.

Neuroscience

Biochem. Pharmacol.

Eur. Neuropsychopharmacol.

Behav. Brain Res.

Drug Alcohol Depend.

Behav. Brain Res.

Eur. J. Pharmacol.

Neuropharmacology

Pharmacol. Ther.

Prog. Neurobiol.

Curr. Opin. Pharmacol.

Brain Res. Rev.

Long-lasting increase in the set point for cocaine self-administration after escalation in rats

Psychopharmacology (Berl.)

Effects of stress and hippocampal NMDA receptor antagonism on recognition memory in rats

Learn. Mem.

The origin and neuronal function of in vivo nonsynaptic glutamate

J. Neurosci.

Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse

Nat. Neurosci.

N-acetyl cysteine-induced blockade of cocaine-induced reinstatement

Ann. N. Y. Acad. Sci.

The role of the dorsal striatum in reward and decision-making

J. Neurosci.

The application of the 5-choice serial reaction time task for the assessment of visual attentional processes and impulse control in rats

Nat. Protoc.

NMDA receptor plasticity in the perirhinal and prefrontal cortices is crucial for the acquisition of long-term object-in-place associative memory

J. Neurosci.

When is the hippocampus involved in recognition memory

J. Neurosci.

Recognition memory for objects, place, and temporal order: a disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex

J. Neurosci.

A temporally distinct role for group I and group II metabotropic glutamate receptors in object recognition memory

Learn. Mem.

Impaired object recognition memory following methamphetamine, but not p-chloroamphetamine- or d-amphetamine-induced neurotoxicity

Neuropsychopharmacology

Methamphetamine influences on recognition memory: comparison of escalating and single-day dosing regimens

Neuropsychopharmacology

Contribution of impulsivity and novelty-seeking to the acquisition and maintenance of MDMA self-administration

Addict. Biol.

Medial frontal cortex mediates perceptual attentional set shifting in the rat

J. Neurosci.

Rule encoding in dorsal striatum impacts action selection

Eur. J. Neurosci.

Methamphetamine neurotoxicity increases brain expression and alters behavioral functions of CB(1) cannabinoid receptors

J. Psychiatr. Res.

Conflict monitoring and cognitive control

Psychol. Rev.

Review article
Chronic methamphetamine self-administration disrupts cortical control of cognition