Methamphetamine-induced alterations in dopamine transporter function

Bennett, Barbara A.; Hollingsworth, Charlotte; Martin, Renée S.; Harp, Jill J.

doi:10.1016/s0006-8993(97)01281-x

Cited by 42 publications

(26 citation statements)

References 42 publications

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“…Methamphetamine increases dopamine neurotransmission mainly by a nonexocytotic impulse-independent release of dopamine into the extracellular space, from an extravesicular, newly synthesized dopamine pool, reversing the direction of the dopamine transporter (DAT) (Kuczenski and Segal, 1994;Nishijima et al, 1996). Thus, methamphetamine's ability to increase extracellular dopamine levels depends on DAT functioning (Bennett et al, 1998;Metzger et al, 2000;Sandoval et al, 2001). Methamphetamine may also increase dopamine synthesis (Nishijima et al, 1996;Larsen et al, 2002), and dopamine-containing vesicles in the cytoplasm of dopamine neurons are affected by methamphetamine administration (Brown et al, 2002;Ugarte et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Histamine H3 Receptor Antagonists Potentiate Methamphetamine Self-Administration and Methamphetamine-Induced Accumbal Dopamine Release

Munzar

Justinová²,

Goldberg³

2004

Neuropsychopharmacol

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Methamphetamine administration increases brain levels of histamine and neuronal histamine attenuates several of methamphetamine's behavioral effects. The role of different subtypes of histamine receptors in this negative feedback, however, remains unclear. There is some evidence on possible involvement of histamine H3 receptors in these actions of methamphetamine. The aim of the present study was to evaluate the effects of two histamine H3 receptor antagonists, clobenpropit and thioperamide, on rewarding and neurochemical effects of methamphetamine utilizing three in vivo methodologies, drug self-administration, drug discrimination, and microdialysis in Sprague-Dawley rats. In rats self-administering methamphetamine intravenously under a fixed-ratio schedule, presession treatment with thioperamide (1.0-3.0 mg/kg, subcutaneous, s.c.) or clobenpropit (1.0-3.0 mg/kg, s.c.) potentiated the reinforcing effects of methamphetamine, as indicated by a dose-dependent increase in responding for a low 0.03 mg/kg dose of methamphetamine, that by itself failed to maintain responding above saline substitution levels, and a decrease in responding for a higher 0.06 mg/kg training dose of methamphetamine. In contrast, neither thioperamide nor clobenpropit treatment increased responding during saline substitution. In other rats trained to discriminate intraperitoneal (i.p.) injection of 1.0 mg/kg methamphetamine from i.p. injection of saline, both thioperamide and clobenpropit (0.3-3.0 mg/kg, s.c.) dose dependently increased methamphetamine-appropriate responding when administered with a low 0.3 mg/kg i.p. dose of methamphetamine, which by itself produced predominantly saline-appropriate responding. However, thioperamide and clobenpropit produced only saline-appropriate responding when administered with saline vehicle. Finally, thioperamide and clobenpropit potentiated methamphetamine-induced elevations in extracellular dopamine levels in the shell of the nucleus accumbens, but did not increase brain dopamine levels when given alone. These findings point to histamine H3 receptors as a new and important receptor system modulating the reinforcing, subjective, and neurochemical actions of methamphetamine.

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Section: Discussionmentioning

confidence: 99%

Histamine H3 Receptor Antagonists Potentiate Methamphetamine Self-Administration and Methamphetamine-Induced Accumbal Dopamine Release

Munzar

Justinová²,

Goldberg³

2004

Neuropsychopharmacol

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“…Likewise, neurotoxicity studies using DA cells in culture would be inconclusive, because efforts to protect DA cells in culture from METH-induced neurotoxicity with DAT blockers have thus far been unsuccessful . In addition, these studies would require prolonged incubations (3-5 d) (Bennett et al, 1993(Bennett et al, , 1998Cubells et al, 1994) at nonphysiological temperatures, a process that would be associated with exceedingly high rates of cell death unrelated to METH. In this regard, however, it is noteworthy that in a recently developed in vitro model, small increments in temperature identical to those used in the present study have been linked to increases in METH-induced DA neurotoxicity, as indexed in that model system .…”

Section: Discussionmentioning

confidence: 99%

Effect of Temperature on Dopamine Transporter Function and Intracellular Accumulation of Methamphetamine: Implications for Methamphetamine-Induced Dopaminergic Neurotoxicity

Xie¹,

McCann

Kim³

et al. 2000

J. Neurosci.

108

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Hyperthermia exacerbates and hypothermia attenuates methamphetamine (METH)-induced dopamine (DA) neurotoxicity. The mechanisms underlying these temperature effects are unknown. Given the essential role of the DA transporter (DAT) in the expression of METH-induced DA neurotoxicity, we hypothesized that the effect of temperature on METH-induced DA neurotoxicity is mediated, at least in part, at the level of the DAT. To test this hypothesis, the effects of small, physiologically relevant temperature changes on DAT function were evaluated in two types of cultured neuronal cells: (1) a neuroblastoma cell line stably transfected with human DAT cDNA and (2) rat embryonic mesencephalic primary cells that naturally express the DAT. Temperatures for studies of DAT function were selected based on core temperature measurements in animals exposed to METH under usual ambient (22°C) and hypothermic (6°C) temperature conditions, where METH neurotoxicity was fully expressed and blocked, respectively. DAT function, determined by measuring accumulation of radiolabeled DA and 1-methyl-4-phenylpyridinium (MPP ϩ ), was found to directly correlate with temperature, with higher levels of substrate uptake at 40°C, intermediate levels at 37°C, and lower levels at 34°C. DAT-mediated accumulation of METH also directly correlated with temperature, with greater accumulation at higher temperatures. These findings indicate that relatively small, physiologically relevant changes in temperature significantly alter DAT function and intracellular METH accumulation, and suggest that the effect of temperature on METHinduced DA neurotoxicity is mediated, at least in part, at the level of the DAT.Key words: dopamine; dopamine transporter; temperature; methamphetamine; MPP ϩ ; neurotoxicityThe psychostimulant methamphetamine (METH) is a potent dopamine (DA) neurotoxin in rodents, nonhuman primates (Gibb et al., 1994;Lew et al., 1998) and, possibly, humans (McCann et al., 1998Volkow et al., 1999). METH administration leads to longlasting reductions in a number of DA axonal markers including DA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid, tyrosine hydroxylase activity, and the DA transporter (DAT). Recent studies indicate that the striatal vesicular monoamine transporter is also reduced on a long-term basis after METH (Frey et al., 1997;Villemagne et al., 1998). Morphological studies indicate that loss of these presynaptic DA axonal markers is related to destruction of DA axons and axon terminals (Ellison et al., 1978;Lorez, 1981;Ricaurte et al., 1982Ricaurte et al., , 1984Bowyer et al., 1994;Broening et al., 1997;Fukumura et al., 1998), generally with sparing of DA nerve cell bodies (Ricaurte et al., 1982;Woolverton et al., 1989; but see Sonsalla et al., 1996;Hirata and Cadet, 1997). The mechanism by which METH induces dopaminergic neurotoxicity is not known. However, there is compelling evidence that the DAT plays an essential role (Marek et al., 1990;Pu et al., 1994;Fumagalli et al., 1998). The DAT is an integral membrane protein of DA neu...

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“…This is of concern because it is well established that high-dose methamphetamine administrations lead to persistent dopaminergic deficits in rodents, nonhuman primates, and humans, as determined by measuring striatal dopamine levels, tyrosine hydroxylase activity, and dopamine transporter function days to months after treatment (Koda and Gibb, 1973;Wagner et al, 1980;Bennett et al, 1998;Schmidt et al, 1985;Seiden, 1985;Wilson et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Age-Dependent Methamphetamine-Induced Alterations in Vesicular Monoamine Transporter-2 Function: Implications for Neurotoxicity

Truong

Wilkins²,

Baudys

et al. 2005

J Pharmacol Exp Ther

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Tens of thousands of adolescents and young adults have used illicit methamphetamine. This is of concern since its high-dose administration causes persistent dopaminergic deficits in adult animal models. The effects in adolescents are less studied. In adult rodents, toxic effects of methamphetamine may result partly from aberrant cytosolic dopamine accumulation and subsequent reactive oxygen species formation. The vesicular monoamine transporter-2 (VMAT-2) sequesters cytoplasmic dopamine into synaptic vesicles for storage and perhaps protection against dopamine-associated oxidative consequences. Accordingly, aberrant VMAT-2 function may contribute to the methamphetamine-induced persistent dopaminergic deficits. Hence, this study examined effects of methamphetamine on VMAT-2 in adolescent (postnatal day 40) and young adult (postnatal day 90) rats. Results revealed that high-dose methamphetamine treatment caused greater acute (within 1 h) decreases in vesicular dopamine uptake in postnatal day 90 versus 40 rats, as determined in a nonmembrane-associated subcellular fraction. Greater basal levels of VMAT-2 at postnatal day 90 versus 40 in this purified fraction seemed to contribute to the larger effect. Basal tissue dopamine content was also greater in postnatal day 90 versus 40 rats. In addition, postnatal day 90 rats were more susceptible to methamphetamine-induced persistent dopaminergic deficits as assessed by measuring VMAT-2 activity and dopamine content 7 days after treatment, even if drug doses were adjusted for age-related pharmacokinetic differences. Together, these data demonstrate dynamic changes in VMAT-2 susceptibility to methamphetamine as a function of development. Implications with regard to methamphetamine-induced dopaminergic deficits, as well as dopamine-associated neurodegenerative disorders such as Parkinson's disease, are discussed.According to the Substance Abuse and Mental Health Services Administration for 2003 (2004), 1.3% of adolescents aged 12 to 17 and 5.2% of young adults aged 18 to 25 have used illicit methamphetamine (METH) at least once in their lifetime. This is of concern because it is well established that high-dose methamphetamine administrations lead to persistent dopaminergic deficits in rodents, nonhuman primates, and humans, as determined by measuring striatal dopamine levels, tyrosine hydroxylase activity, and dopamine transporter function days to months after treatment (Koda and Gibb, 1973;Wagner et al., 1980;Bennett et al., 1998;Schmidt et al., 1985;Seiden, 1985;Wilson et al., 1996).Most studies of methamphetamine and its actions have involved adult animal models. However, given the prevalence of methamphetamine use among young people, increasing attention has focused on effects of the stimulant in adolescent animal models. For example, Cappon et al. (1997) demonstrated that multiple high-dose administrations of methamphetamine reduce striatal dopamine levels in postnatal day 60, but not postnatal day 20, rats. Similarly, this highdose methamphetamine regimen lead...

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Methamphetamine-induced alterations in dopamine transporter function

Cited by 42 publications

References 42 publications

Histamine H3 Receptor Antagonists Potentiate Methamphetamine Self-Administration and Methamphetamine-Induced Accumbal Dopamine Release

Histamine H3 Receptor Antagonists Potentiate Methamphetamine Self-Administration and Methamphetamine-Induced Accumbal Dopamine Release

Effect of Temperature on Dopamine Transporter Function and Intracellular Accumulation of Methamphetamine: Implications for Methamphetamine-Induced Dopaminergic Neurotoxicity

Age-Dependent Methamphetamine-Induced Alterations in Vesicular Monoamine Transporter-2 Function: Implications for Neurotoxicity

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