Alterations in cortical activity of male methamphetamine abusers performing an empathy task: fMRI study

Kim, Yang-Tae; Lee, Jaejun; Song, Hyohak; Kim, Joohyun; Kwon, Dohoon; Kim, Myoung-Nam; Yoo, Done-Sik; Lee, Hui Joong; Kim, Hye-Jung; Chang, Yongmin

doi:10.1002/hup.1083

Cited by 39 publications

(29 citation statements)

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“…Hippocampus-dependent cognitive impairments in methamphetamine-abusing subjects can be attributed to methamphetamine-induced alterations in structural and functional plasticity of hippocampal neurons. For example, human imaging studies show reduced hippocampal volume, particularly gray matter volume, and decreased hippocampal responsiveness in chronic methamphetamine users (Thompson et al, 2004, Kim et al, 2010, Schwartz et al, 2010, Daumann et al, 2011, Nakama et al, 2011, Orikabe et al, 2011, Morales et al, 2012), indicating maladaptive hippocampal networking in methamphetamine-exposed individuals. Postmortem analyses in human brain tissue confirms that chronic methamphetamine use produces neurotoxicity in the hippocampus (Kitamura, 2009, Kitamura et al, 2010), which suggests an association between hippocampal dysfunction and toxicity in methamphetamine addicts.…”

Section: Introductionmentioning

confidence: 99%

Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

2015

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Methamphetamine exposure reduces hippocampal long-term potentiation (LTP) and neurogenesis and these alterations partially contribute to hippocampal maladaptive plasticity. The potential mechanisms underlying methamphetamine-induced maladaptive plasticity were identified in the present study. Expression of brain-derived neurotrophic factor (BDNF; a regulator of LTP and neurogenesis), and its receptor tropomyosin-related kinase B (TrkB) were studied in the dorsal and ventral hippocampal tissue lysates in rats that intravenously self-administered methamphetamine in a limited access (1 h/day) or extended access (6 h/day) paradigm for 17 days post baseline sessions. Extended access methamphetamine enhanced expression of BDNF with significant effects observed in the dorsal and ventral hippocampus. Methamphetamine-induced enhancements in BDNF expression were not associated with TrkB receptor activation as indicated by phospho (p)-TrkB-706 levels. Conversely, methamphetamine produced hypophosphorylation of NMDA receptor subunit 2B (GluN2B) at Tyr-1472 in the ventral hippocampus, indicating reduced receptor activation. In addition, methamphetamine enhanced expression of anti-apoptotic protein Bcl-2 and reduced pro-apoptotic protein Bax levels in the ventral hippocampus, suggesting a mechanism for reducing cell death. Analysis of Akt, a pro-survival kinase that suppresses apoptotic pathways and pAkt at Ser-473 demonstrated that extended access methamphetamine reduces Akt expression in the ventral hippocampus. These data reveal that alterations in Bcl-2 and Bax levels by methamphetamine were not associated with enhanced Akt expression. Given that hippocampal function and neurogenesis vary in a subregion-specific fashion, where dorsal hippocampus regulates spatial processing and has higher levels of neurogenesis, whereas ventral hippocampus regulates anxiety-related behaviors, these data suggest that methamphetamine self-administration initiates distinct allostatic changes in hippocampal subregions that may contribute to the altered synaptic activity in the hippocampus, which may underlie enhanced negative affective symptoms and perpetuation of the addiction cycle.

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Section: Introductionmentioning

confidence: 99%

Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

2015

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“…Converging lines of evidence from clinical and preclinical studies have revealed that methamphetamine dependence is linked to a decreased volume of limbic-related structures (Schwartz et al, 2010;Simon et al, 2010), altered hippocampal morphology Kim et al, 2010), and hippocampal-related deficits in learning and memory (Rogers et al, 1999(Rogers et al, , 2008. Given that the hippocampus is essentially involved in learning and memory processes (Black et al, 1977;Morris et al, 1982;Eichenbaum et al, 1992;Riedel et al, 1999;Scoville and Milner, 2000;Burgess et al, 2002) and mounting evidence that suggests a role of an important form of hippocampal plasticity, namely adult hippocampal neurogenesis in hippocampus-dependent learning and memory (van Praag et al, 1999;Shors et al, 2001;Jessberger et al, 2009; for reviews, see Leuner et al, 2006;Kim et al, 2011), we wished to determine whether methamphetamine-induced inhibition of hippocampal neurogenesis contributes to methamphetamine-induced impairments in hippocampusdependent cognitive behaviors.…”

Section: Introductionmentioning

confidence: 99%

Levels of Neural Progenitors in the Hippocampus Predict Memory Impairment and Relapse to Drug Seeking as a Function of Excessive Methamphetamine Self-Administration

Recinto

Samant

Chávez

et al. 2011

Neuropsychopharmacol

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Methamphetamine affects the hippocampus, a brain region crucial for learning and memory, as well as relapse to drug seeking. Rats self-administered methamphetamine for 1 h twice weekly (intermittent-short-I-ShA), 1 h daily (limited-short-ShA), or 6 h daily (extended-long-LgA) for 22 sessions. After 22 sessions, rats from each access group were withdrawn from self-administration and underwent spatial memory (Y-maze) and working memory (T-maze) tests followed by extinction and reinstatement to methamphetamine seeking or received one intraperitoneal injection of 5-bromo-2'-deoxyuridine (BrdU) to label progenitors in the hippocampal subgranular zone (SGZ) during the synthesis phase. Two-hour-old and 28-day-old surviving BrdU-immunoreactive cells were quantified. I-ShA rats performed better on the Y-maze and had a greater number of 2-h-old SGZ BrdU cells than nondrug controls. LgA rats, but not ShA rats, performed worse on the Y- and T-maze and had a fewer number of 2-h-old SGZ BrdU cells than nondrug and I-ShA rats, suggesting that new hippocampal progenitors, decreased by methamphetamine, were correlated with impairment in the acquisition of new spatial cues. Analyses of addiction-related behaviors after withdrawal and extinction training revealed methamphetamine-primed reinstatement of methamphetamine-seeking behavior in all three groups (I-ShA, ShA, and LgA), and this effect was enhanced in LgA rats compared with I-ShA and ShA rats. Protracted withdrawal from self-administration enhanced the survival of SGZ BrdU cells, and methamphetamine seeking during protracted withdrawal enhanced Fos expression in the dentate gyrus and medial prefrontal cortex in LgA rats to a greater extent than in ShA and I-ShA rats. These results indicate that changes in the levels of the proliferation and survival of hippocampal neural progenitors and neuronal activation of hippocampal granule cells predict the effects of methamphetamine self-administration (limited vs extended access) on cognitive performance and relapse to drug seeking and may contribute to the impairments that perpetuate the addiction cycle.

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“…For example, one human study found that hippocampal metabolic and structural measures predict the performance on a vigilance test of sustained attention, which could be related to cognitive deficits observed in MA abusers (9). Other human studies suggested that hippocampus is a brain region related to episodic memory and empathy; the damage in this area in MA abusers may contribute to altered emotional experience and misunderstanding of others, leading to deteriorated interpersonal communication and social interactions in this patient population (7, 8). Animal studies found that extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) signaling pathway in the hippocampus might be involved in MA induced spatial memory changes (10).…”

Section: Introductionmentioning

confidence: 95%

“…Growing evidence from both human (7–9) and animal (10–12) studies have found that MA users demonstrate dysfunction in these hippocampal functions and are linked to the clinical criteria of substance use disorders. Gardner et al reported acute hippocampal toxicity from structural MRI, following chronic use of MA (13).…”

Section: Introductionmentioning

confidence: 99%

Hippocampal volume reduction in female but not male recent abstinent methamphetamine users

Quan

Zhuang

et al. 2015

Behavioural Brain Research

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Background and Aims Growing evidence suggests abnormalities in brain morphology including hippocampal structure in patients with methamphetamine (MA) dependence. Yet little is known about the possible gender difference. This study was performed to examine hippocampal volume in abstinent male and female MA users, and to further explore its relationship with cognitive function. Methods 27 abstinent MA users (19 males and 8 females) with average 5.75 months of duration and 29 healthy controls (19 males and 10 females) age 18 to 45 years old were recruited for clinical assessment and imaging scan. FreeSurfer was used to segment the hippocampus bilaterally, and hippocampal volumes were extracted for group and gender comparisons. Cognitive function was measured using the CogState Battery Chinese language version (CSB-C). Results Analysis of covariance (ANCOVA) controlling for education showed a significant group by gender interaction for right hippocampal relative volume adjusted for total brain size (p=0.002). Female patients showed significantly less volume compared with female healthy controls; there was no significant difference in volume between male patients and male healthy controls. Within female patients, there were significant negative relationships between right hippocampal volume and average dose of MA use (p=0.001), as well as the total error scores on the Continuous Paired Association Learning Task (CPAL) in CSB-C (p=0.013). Conclusions There seems to be a gender difference in how MA affects hippocampal volume and cognitive function in abstinent MA users. Hippocampus might be an important treatment target for cognitive improvement and functional recovery in this patient population, especially in females.

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Alterations in cortical activity of male methamphetamine abusers performing an empathy task: fMRI study

Abstract: Functional impairments in the empathic neural network caused by MA may contribute to the misunderstanding of others and to the erosion of social interactions in MA abusers.

Cited by 39 publications

References 47 publications

Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

Levels of Neural Progenitors in the Hippocampus Predict Memory Impairment and Relapse to Drug Seeking as a Function of Excessive Methamphetamine Self-Administration

Hippocampal volume reduction in female but not male recent abstinent methamphetamine users

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