Review articleChronic methamphetamine self-administration disrupts cortical control of cognition
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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