Long-lasting depletions of striatal dopamine and loss of dopamine uptake sites following repeated administration of methamphetamine

Wagner, George C.; Ricaurte, George A.; Seiden, Lewis S.; Schuster, Charles R.; Miller, Richard J.; Westley, John

doi:10.1016/0006-8993(80)91265-2

Cited by 499 publications

(286 citation statements)

References 13 publications

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“…In preclinical studies, high-dose MA produces neurotoxic changes in striatal dopaminergic cells as well as deficits in striatal tyrosine hydroxylase activity, DA concentrations, and DAT levels (Davidson et al, 2001;Harvey et al, 2000;Robinson et al, 1990;Sabol et al, 2001;Wagner et al, 1980). Clinical imaging studies have also found significant deficits in dopaminergic function among chronic MA users, including reductions in DAT density (Volkow et al, 2001b) and DA receptor occupancy (Volkow et al, 2001a;Volkow et al, 2001c), which are thought to contribute to the dysphoric symptoms that accompany MA dependence and withdrawal.…”

Section: Discussionmentioning

confidence: 99%

Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence

Shoptaw

Heinzerling

Rotheram-Fuller

et al. 2008

Drug and Alcohol Dependence

136

129

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Objective-To compare bupropion to placebo for reducing methamphetamine (MA) use, increasing retention, and reducing the severity of depressive symptoms and MA cravings. A secondary objective compared bupropion to placebo for reducing cigarette smoking among MA dependent participants.Methods-Following a 2-week, non-medication baseline screening period, 73 treatment-seeking MA dependent participants were randomly assigned to bupropion sustained release (150 mg twice daily; N=36) or placebo (twice daily; N=37) for 12-weeks under double blind conditions. Participants attended clinic thrice weekly to provide urine samples analyzed for MA-metabolite, to complete research measures and assessments, and to receive contingency management and weekly cognitive behavioral therapy sessions.Results-There were no statistically significant effects for bupropion relative to placebo on MA use verified by urine drug screens, for reducing the severity of depressive symptoms or MA cravings, or on study retention. In a post hoc analysis, there was a statistically significant effect of bupropion treatment on MA use among participants with lighter (0-2 MA-positive urines), but not heavier (3-6 MA-positive urines) MA use during baseline (OR=2.81, 95% CI=1.61-4.93, p<0.001 for MA-free week with bupropion among light users). Bupropion treatment was also associated with significantly reduced cigarette smoking, by almost 5 cigarettes per day (p=0.0002).Conclusion-Bupropion was no more effective than placebo in reducing MA use in planned analyses, though bupropion did reduce cigarette smoking. Post hoc findings of an effect for bupropion among baseline light, but not heavy, MA users suggests further evaluation of bupropion for light MA users is warranted.

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Section: Discussionmentioning

confidence: 99%

Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence

Shoptaw

Heinzerling

Rotheram-Fuller

et al. 2008

Drug and Alcohol Dependence

136

129

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“…In both mice and rats, acute repeated injections of METH produce long-lasting decreases in DA levels [145, 149-153], and long-term reductions in several DA markers, such as TH [144, 154, 155], DAT [152, 156, 157], and VMAT-2 [155, 157-159] within the striatum. Morphological studies demonstrate that the persistent loss of integrity of DA biochemical markers is due to the degeneration of DA axon terminals [145-149].…”

Section: Methamphetamine-induced Dopaminergic Toxicitymentioning

confidence: 99%

The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity

Ferrucci

Giorgi

Bartalucci

et al. 2013

Current Neuropharmacology

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The activity of locus coeruleus (LC) neurons has been extensively investigated in a variety of behavioural states. In fact this norepinephrine (NE)-containing nucleus modulates many physiological and pathological conditions including the sleep-waking cycle, movement disorders, mood alterations, convulsive seizures, and the effects of drugs such as psychostimulants and opioids. This review focuses on the modulation exerted by central NE pathways on the behavioural and neurotoxic effects produced by the psychostimulant methamphetamine, essentially the modulation of the activity of mesencephalic dopamine (DA) neurons. In fact, although NE in itself mediates some behavioural effects induced by methamphetamine, NE modulation of DA release is pivotal for methamphetamine-induced behavioural states and neurotoxicity. These interactions are discussed on the basis of the state of the art of the functional neuroanatomy of central NE- and DA systems. Emphasis is given to those brain sites possessing a remarkable overlapping of both neurotransmitters.

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“…The neurotoxic effects are evidenced by long-term depletions in striatal dopamine (DA) and serotonin (5-HT) concentrations, and their uptake sites (Friedman et al, 1998;Ricaurte et al, 1982;Wagner et al, 1980), decreases in tryptophan and tyrosine hydroxylase activity (Bakhit et al, 1981), and cell loss (Deng et al, 2007;Sonsalla et al, 1996;Thiriet et al, 2005;Yu et al, 2004;Zhu et al, 2006). In addition to the hypotheses of oxidative stress and apoptosis as mechanisms of METH-induced neurotoxicity (for review, see Davidson et al, 2001;Kita et al, 2003;Quinton and Yamamoto, 2006), increases in the extracellular concentrations of glutamate (GLU) have been also suggested to play an important role (Abekawa et al, 1994;Nash and Yamamoto, 1992;Sonsalla et al, 1989;Stephans and Yamamoto, 1994).…”

Section: Introductionmentioning

confidence: 99%

Chronic stress enhances methamphetamine‐induced extracellular glutamate and excitotoxicity in the rat striatum

Tata

Yamamoto

2008

Synapse

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Striking parallels exist between the neurochemical and toxic effects of stress and methamphetamine. Despite these similarities, no studies have examined how stress may promote the toxic effects of methamphetamine (METH). The current study tested the hypothesis that chronic stress enhances METH toxicity by augmenting glutamate (GLU) release and excitotoxicity in response to METH administration. Adult male Sprague-Dawley rats were exposed to 10 days of unpredictable stress and then received either saline or METH (7.5 mg/kg, i.p., once every 2 h × four injections). Prior exposure to unpredictable stress acutely enhanced the striatal extracellular GLU concentrations in response to METH, and eventually caused proteolysis of the cytoskeleton protein spectrin. Administration of the corticosterone synthesis inhibitor, metyrapone (25 mg/kg, i.p., prior to each stressor), during unpredictable stress attenuated the enhanced striatal GLU release in response to METH, blocked spectrin proteolysis, and attenuated METH-associated toxicity measured by long-term depletions in the dopamine and serotonin tissue content as well as depletions in dopamine and serotonin transporter immunoreactivity of the striatum. In summary, prior exposure to unpredictable stress enhances METH-induced elevations of GLU in the striatum, resulting in long-term excitotoxic damage and an augmentation of damage to dopamine and serotonin terminals. These studies provide a neurochemical basis for how stress contributes to the deleterious effects of METH abuse.

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Long-lasting depletions of striatal dopamine and loss of dopamine uptake sites following repeated administration of methamphetamine

Cited by 499 publications

References 13 publications

Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence

Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence

The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity

Chronic stress enhances methamphetamine‐induced extracellular glutamate and excitotoxicity in the rat striatum

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