Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers

Johanson, Chris E.; Frey, Kirk A.; Lundahl, Leslie H.; Keenan, P. A.; Lockhart, Nancy; Koeppe, Robert A.; Kilbourn, Michael R.; Robbins, Trevor W.; Schuster, Charles R.

doi:10.1007/s00213-006-0393-4

Cited by 49 publications

(84 citation statements)

References 19 publications

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“…The extent to which those characterizations can be generalized for interpreting METH's effects on human brain neurochemistry has remained tenuous for many years. Now, as was observed in animal studies, some METHassociated effects on the striatal dopamine (DA) system have also been consistently shown in humans, in vivo, with PET imaging, namely, lower dopamine transporter (DAT) ligand binding (15-30%) (McCann et al, 1998;Sekine et al, 2001;Volkow et al, 2001;Wang et al, 2004;Johanson et al, 2006). A post-mortem study has also shown lower DAT ligand binding, in addition to reductions in DA and tyrosine hydroxylase protein content (Wilson et al, 1996).…”

Section: Introductionmentioning

confidence: 67%

“…After several months of abstinence, those individuals showed 15-30% lower striatal DAT ligand binding. The changes in the DAT were rather limited as suggested by the extensive overlap of individual values shown in the scatter plots of METH and control groups (Volkow et al, 2001;Johanson et al, 2006). Similarly, a recent PET imaging study that assessed both DAT and VMAT ligand binding in METH-dependent individuals reported lower values of only 15 and 10%, respectively, compared to controls (Johanson et al, 2006).…”

Section: Brain Alterationsmentioning

confidence: 95%

“…The changes in the DAT were rather limited as suggested by the extensive overlap of individual values shown in the scatter plots of METH and control groups (Volkow et al, 2001;Johanson et al, 2006). Similarly, a recent PET imaging study that assessed both DAT and VMAT ligand binding in METH-dependent individuals reported lower values of only 15 and 10%, respectively, compared to controls (Johanson et al, 2006). Since only subjects who met DSM-IV criteria for METH dependence (ie not infrequent or short-term abusers) were imaged in these studies, it is not likely that individuals with a greater magnitude or duration of exposure will be characterized, in vivo, in the future.…”

Section: Brain Alterationsmentioning

confidence: 99%

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Long-Term Methamphetamine Administration in the Vervet Monkey Models Aspects of a Human Exposure: Brain Neurotoxicity and Behavioral Profiles

Melega

Jorgensen

Laćan

et al. 2007

Neuropsychopharmacol

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Methamphetamine (METH)-associated alterations in the human striatal dopamine (DA) system have been identified with positron emission tomography (PET) imaging and post-mortem studies but have not been well correlated with behavioral changes or cumulative METH intake. Animal studies that model some aspects of human long-term METH abuse can establish dose-dependency profiles of both behavioral changes and potential brain neurotoxicities for identifying consequences of particular cumulative exposures. Based on parameters from human and our monkey pharmacokinetic studies, we modeled a prevalent human METH exposure of daily multiple doses in socially housed vervet monkeys. METH doses were escalated over 33 weeks, with final dosages resulting in estimated peak plasma METH concentrations of 1-3 mM, a range measured in human abusers. With larger METH doses, progressive increases in abnormal behavior and decreases in social behavior were observed on 'injection' days. Anxiety increased on 'no injection' days while aggression decreased throughout the study. Thereafter, during 3 weeks abstinence, differences in baseline vs post-METH behaviors were not observed. Post-mortem analysis of METH brains showed 20% lower striatal DA content while autoradiography studies of precommissural striatum showed 35% lower [ 3 H]WIN35428 binding to the DA transporter. No statistically significant changes were detected for [ 3 H]dihydrotetrabenazine binding to the vesicular monoamine transporter (METH-lower by 10%) or for [ 3 H]SCH 23390 and [ 3 H]raclopride binding to DA D1 and D2 receptors, respectively. Collectively, this long-term, escalating dose METH exposure modeling a human abuse pattern, not associated with high-dose binges, resulted in dose-dependent behavioral effects and caused persistent changes in presynaptic striatal DA system integrity.

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Section: Introductionmentioning

confidence: 67%

Section: Brain Alterationsmentioning

confidence: 95%

Section: Brain Alterationsmentioning

confidence: 99%

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Long-Term Methamphetamine Administration in the Vervet Monkey Models Aspects of a Human Exposure: Brain Neurotoxicity and Behavioral Profiles

Melega

Jorgensen

Laćan

et al. 2007

Neuropsychopharmacol

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“…In a PET imaging investigation of "heavy" MA users, the striatal [ 11 C] DTBZ binding was decreased by 10%, even after at least 3 months of abstinence, reflecting the long-lasting effect of MA on VMAT2 [46] . And in the study of Boileau et al [43] , who used human subjects to measure striatal [ 11 C] DTBZ binding after an acute oral dose of amphetamine (AMPH), a slight decrease of [ 11 C] DTBZ binding was also found.…”

Section: Pet Studies Of Vesicular Monoamine Transportermentioning

confidence: 99%

Brain dopaminergic system changes in drug addiction: a review of positron emission tomography findings

et al. 2014

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Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction remains unclear. Positron emission tomography (PET) is the fi rst technology used for in vivo measurement of components of the dopaminergic system in the human brain. In this article, we review the major fi ndings from PET imaging studies on the involvement of DA in drug addiction, including presynaptic DA synthesis, vesicular monoamine transporter 2, the DA transporter, and postsynaptic DA receptors. These results have corroborated the role of DA in addiction and increased the understanding of its underlying mechanisms.Keywords: dopamine; dopaminergic system; drug addiction; positron emission tomography ·Review· Brain Dopaminergic System Dopamine (DA) is a catecholamine neurotransmitter in the nervous system. It has many functions in the brain, including punishment, reward, voluntary movement, mood, attention, motivation, sleep, working memory, and learning [1] .DA is synthesized by the hydroxylation and decarboxylation of L-tyrosine in DA neurons and, before being released into the synapse in response to an action potential, it is stored within presynaptic vesicles (Fig. 1). The action of DA occurs by binding to postsynaptic DA receptors, resulting in the formation of second messengers. There are fi ve subtypes of DA receptors, which can be grouped into two classes or families: D1-like and D-2 like [1,2] . The D1-like receptor family comprises the D1 and D5 receptors, encoded by genes with no introns, acting by way of Gs-proteins and activating adenylyl cyclase, thus increasing cAMP production [3,4] .The D2-like receptor family comprises the D2, D3, and D4 receptors, encoded by genes containing introns. D2-like receptors act via Gi-proteins, inhibit adenylyl cyclase activity, and thus decrease cAMP activity [3,5] .The action of DA in the synapse is terminated primarily by reuptake to the presynaptic membrane through the dopamine transporter (DAT) [6] . Otherwise, DA is partially removed by oxidation by monoamine oxidase orcatechol-O-methyltransferase in the synaptic cleft (Fig. 1).T h e d o p a m i n e r g i c n e u r o n s , w h o s e p r i m a r y neurotransmitter is DA, interconnect many areas of the brain to form a system which originates in the substantia nigra (SN) pars compacta, ventral tegmental area (VTA), and hypothalamus. The dopaminergic system is typically divided into four major pathways: mesocortical (from the VTA to the frontal cortex), mesolimbic (from the VTA to the nucleus accumbens), nigrostriatal (from the SN to the striatum), and tuberoinfundibular (from the hypothalamus to the pituitary gland). The mesostriatal and mesocortical pathways are currently recognized to contribute most to drug addiction [7] . Neurosci Bull October 1, 2014, 30(5): 765-776 766 Drug AddictionThe term addiction is derived from the Latin verb addicere, which referred to the Roman court action of binding a person to another. From the 17th century, addiction has been used to refer to psychoactive substances (...

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“…Human neuroimaging studies have shown that chronic methamphetamine users display deficits in striatal dopamine receptors (Lee et al, 2009), dopamine transporters (McCann et al, 2008), and vesicular monoamine transporters (Johanson et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment

Robertson

Ishibashi

Chudzynski

et al. 2015

Neuropsychopharmacol

108

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Methamphetamine use disorder is associated with striatal dopaminergic deficits that have been linked to poor treatment outcomes, identifying these deficits as an important therapeutic target. Exercise attenuates methamphetamine-induced neurochemical damage in the rat brain, and a preliminary observation suggests that exercise increases striatal D2/D3 receptor availability (measured as nondisplaceable binding potential (BP ND )) in patients with Parkinson's disease. The goal of this study was to evaluate whether adding an exercise training program to an inpatient behavioral intervention for methamphetamine use disorder reverses deficits in striatal D2/D3 receptors. Participants were adult men and women who met DSM-IV criteria for methamphetamine dependence and were enrolled in a residential facility, where they maintained abstinence from illicit drugs of abuse and received behavioral therapy for their addiction. They were randomized to a group that received 1 h supervised exercise training (n = 10) or one that received equal-time health education training (n = 9), 3 days/week for 8 weeks. They came to an academic research center for positron emission tomography (PET) using [ 18 F]fallypride to determine the effects of the 8-week interventions on striatal D2/D3 receptor BP ND . At baseline, striatal D2/D3 BP ND did not differ between groups. However, after 8 weeks, participants in the exercise group displayed a significant increase in striatal D2/D3 BP ND , whereas those in the education group did not. There were no changes in D2/D3 BP ND in extrastriatal regions in either group. These findings suggest that structured exercise training can ameliorate striatal D2/D3 receptor deficits in methamphetamine users, and warrants further evaluation as an adjunctive treatment for stimulant dependence.

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Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers

Cited by 49 publications

References 19 publications

Long-Term Methamphetamine Administration in the Vervet Monkey Models Aspects of a Human Exposure: Brain Neurotoxicity and Behavioral Profiles

Long-Term Methamphetamine Administration in the Vervet Monkey Models Aspects of a Human Exposure: Brain Neurotoxicity and Behavioral Profiles

Brain dopaminergic system changes in drug addiction: a review of positron emission tomography findings

Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment

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