Formation of 6-hydroxydopamine in caudate nucleus of the rat brain after a single large dose of methylamphetamine

Seiden, Lewis S.; Vosmer, Georgetta

doi:10.1016/0091-3057(84)90125-4

Cited by 219 publications

(76 citation statements)

References 16 publications

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“…In addition, C ORE TEM P hypothermia could decrease and hyperthermia could increase free radical formation such as 6-OH DA, 5,7-DHT, and NO (Halliwell, 1992). At least some, if not all, of these free radicals are theorized to participate in amphetamine-induced neurotoxicity (Seiden and Vosmer, 1984;Commins et al, 1987a;Dawson et al, 1993;Cadet et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat

1998

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The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) is a drug of abuse and has been shown to be neurotoxic to 5-HT terminals in many species. MDMAengendered neurotoxicity has been shown to be affected by both ambient temperature and core body temperature. We now report that small (2°C) changes in ambient temperature produce changes in core temperature in MDMA-treated rats, but the same changes in ambient temperature do not affect core temperature of saline-treated animals. Furthermore, increases in core temperature of MDMA-treated animals increase neurotoxicity. Rats were given MDMA (20 or 40 mg/kg) or saline and placed in an ambient temperature of 20, 22, 24, 26, 28, or 30°C using a novel temperature measurement apparatus that controls ambient temperature Ϯ0.5°C. Two weeks after MDMA treatment, the rats were killed, and regional 5-HT and 5-hydroxyindole acetic acid levels were analyzed as a measure of neurotoxicity. Rats treated with MDMA at 20 and 22°C showed a hypothermic core temperature response. Treatment with MDMA at 28 and 30°C produced a hyperthermic response. At ambient temperatures of 20-24°C, neurotoxicity was not observed in the frontal cortex, somatosensory cortex, hippocampus, or striatum. At ambient temperatures of 26-30°C, neurotoxicity was seen and correlated with core temperature in all regions examined. These data indicate that ambient temperature has a significant affect on MDMA neurotoxicity, core temperature, and thermoregulation in rats. This finding has implications on both the temperature dependence of the mechanism of MDMA neurotoxicity and human use because fatal hyperthermia is associated with MDMA use in humans.

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Section: Discussionmentioning

confidence: 99%

Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat

1998

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“…These exaggerated responses to the 1,000 µ M MA dose may provide some insight into the mechanistic bases for the sex differences observed. A proposed mechanism for amphetamines involves that of a reversal in the action of the DA transporter, resulting in increased DA output and an inhibition of DA uptake [31,32,33,34,35]. This inhibition of DA uptake can represent a rapid effect of MA upon DA nerve terminals [36].…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Methamphetamine-Evoked Striatal Dopamine Output Are Abolished following Gonadectomy: Comparisons with Potassium-Evoked Output and Responses in Prepubertal Mice

Dluzen

Salvaterra²

2005

Neuroendocrinology

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Sex differences are reported for methamphetamine (MA)-induced neurotoxicity of the nigrostriatal dopaminergic system. In an attempt to understand some of the bases for these differences, we investigated MA-evoked dopamine (DA) responses from superfused striatal tissue fragments of intact and male and female CD-1 mice. These responses were compared with that of gonadectomized mice, potassium-evoked DA responses in intact mice and responses in prepubertal mice. In experiment 1, DA responses were tested using infusion of MA at doses of 1, 10, 100 and 1,000 µM. In intact mice, mean peak MA-evoked DA responses were consistently increased and significantly greater in male vs. female mice at the 1,000 µM dose. No such significant differences were observed between gonadectomized male vs. female mice (experiment 2). In contrast to MA, potassium-stimulated DA responses were increased in intact female mice, with statistically significant differences at doses of 30 and 60 mM (experiment 3). No statistically significant differences between intact prepubertal male and female mice were obtained in response to a 1,000 µM dose of MA (experiment 4) or to a 60 mM dose of potassium (experiment 5). These results indicate that intact male mice show greater sensitivity to MA-evoked DA output. This sex difference is abolished following gonadectomy, is not observed with potassium, nor is it present in prepubertal mice. The increased sensitivity to MA shown by intact males may be related to the greater degree of striatal dopaminergic neurotoxicity observed in male mice in response to this psychostimulant and appears to be attributable to differences in gonadal steroid hormones between male and female mice.

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“…Acute METH intoxication might be due to an increase in the levels of synaptic striatal dopamine (DA) (Pereira et al, 2002(Pereira et al, , 2004, whereas long-term effects could be secondary to persistent perturbations in monoaminergic systems (Wagner et al, 1980). METH-induced neurotoxicity in monoaminergic systems has been observed in rats given single large doses (in the range of 20-100 mg/kg) (Cappon et al, 2000;Fukumura et al, 1998;Imam and Ali, 2001;Seiden and Vosmer, 1984) or 5-10 mg/kg, given four times at intervals of 2 h (Chapman et al, 2001). Toxicity in dopaminergic systems was also reported in mice given either a single dose of METH (25 mg/kg) (Hayashi et al, 2001) or multiple doses, with the animals receiving four injections of METH varying from 5 to 10 mg/kg at 2-h intervals (Ali et al, 1994;Fornai et al, 2004;Thomas et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Single or multiple injections of methamphetamine increased dopamine turnover but did not decrease tyrosine hydroxylase levels or cleave caspase‐3 in caudate‐putamen

Pereira

Lourenço

Borges

et al. 2006

Synapse

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Methamphetamine (METH), leading to striatal dopamine (DA) nerve terminal toxicity in mammals, is also thought to induce apoptosis of striatal neurons in rodents. We investigated the acute effects induced by multiple injections of METH (4 3 5 mg/kg, i.p.) at 2-h intervals or a single injection of METH (20 mg/kg, i.p.) on terminal dopaminergic toxicity markers, including DA levels, DA turnover, and tyrosine hydroxylase (TH) immunoreactivity in rat caudate-putamen (CPu). We further investigated whether both treatment paradigms would change Bax and activate caspase-3 expression, thus triggering striatal apoptotic mitochondria-dependent biochemical cascades. The first injection of METH (5 mg/kg, i.p.) produced a significant release of DA that peaked 30 min and stayed above control levels up to 1.5 h within CPu. In another set of experiments, rats were killed 1 and 24 h following the last injection, for tissue DA and metabolite content measurement and Western blot analysis (24 h). Multiple doses induced DA depletion and increased turnover at both endpoints. Singledose METH reproduced these effects at 24 h; however, turnover was significantly higher than that evoked by the multiple doses at 24 h. Although both paradigms evoked similar DA depletion, however, none of the dosing regimens induced changes in TH expression at 24 h. The former paradigm produced an increase in Bax expression in CPu not sufficient to induce cleavage of caspase-3 proenzyme at 24 h. This study suggests that both paradigm induced changes in striatal dopaminergic markers that are independent of terminal degeneration and striatal apoptotic mitochondria-dependent caspase-3 driven cascade within 24 h.

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Formation of 6-hydroxydopamine in caudate nucleus of the rat brain after a single large dose of methylamphetamine

Cited by 219 publications

References 16 publications

Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat

Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat

Sex Differences in Methamphetamine-Evoked Striatal Dopamine Output Are Abolished following Gonadectomy: Comparisons with Potassium-Evoked Output and Responses in Prepubertal Mice

Single or multiple injections of methamphetamine increased dopamine turnover but did not decrease tyrosine hydroxylase levels or cleave caspase‐3 in caudate‐putamen

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