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Selective vulnerability in striosomes and in the nigrostriatal dopaminergic pathway after methamphetamine administration : early loss of TH in striosomes after methamphetamine.

Granado N, Ares-Santos S, O'Shea E, Vicario-Abejón C, Colado MI, Moratalla R - Neurotox Res (2009)

Bottom Line: In addition, the drug caused a reduction in TH- and DAT-immunoreactivity when compared to saline-treated animals.Interestingly, there was a significantly greater loss of TH- and DAT-immunoreactivity in striosomes than in the matrix.In contrast, METH did not decrease TH- or DAT-immunoreactivity in the nucleus accumbens.

View Article: PubMed Central - PubMed

Affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avda. Dr. Arce 37, 28002, Madrid, Spain.

ABSTRACT
Methamphetamine (METH), a commonly abused psychostimulant, causes dopamine neurotoxicity in humans, rodents, and nonhuman primates. This study examined the selective neuroanatomical pattern of dopaminergic neurotoxicity induced by METH in the mouse striatum. We examined the effect of METH on tyrosine hydroxylase (TH) and dopamine transporter (DAT) immunoreactivity in the different compartments of the striatum and in the nucleus accumbens. The levels of dopamine and its metabolites, 3,4-dihidroxyphenylacetic acid and homovanillic acid, as well as serotonin (5-HT) and its metabolite, 5-hydroxyindolacetic acid, were also quantified in the striatum. Mice were given three injections of METH (4 mg/kg, i.p.) at 3 h intervals and sacrificed 7 days later. This repeated METH injection induced a hyperthermic response and a decrease in striatal concentrations of dopamine and its metabolites without affecting 5-HT concentrations. In addition, the drug caused a reduction in TH- and DAT-immunoreactivity when compared to saline-treated animals. Interestingly, there was a significantly greater loss of TH- and DAT-immunoreactivity in striosomes than in the matrix. The predominant loss of dopaminergic terminals in the striosomes occurred along the rostrocaudal axis of the striatum. In contrast, METH did not decrease TH- or DAT-immunoreactivity in the nucleus accumbens. These results provide the first evidence that compartments of the mouse striatum, striosomes and matrix, and mesolimbic and nigrostriatal pathways have different vulnerability to METH. This pattern is similar to that observed with other neurotoxins such as MPTP, the most widely used model of Parkinson's disease, in early Huntington's disease and hypoxic/ischemic injury, suggesting that these conditions might share mechanisms of neurotoxicity.

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Related in: MedlinePlus

Effect of METH on mouse rectal temperature. Repeated METH administration (4 mg/kg, i.p., every 3 h, 3×) produced a decrease in rectal temperature of the animals after the first injection and an increase in the rectal temperature, peaking 30 min after the second and third injections. The arrows indicate the time of drug injection. Data represent mean ± S.E.M., n = 6 animals/group
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Fig1: Effect of METH on mouse rectal temperature. Repeated METH administration (4 mg/kg, i.p., every 3 h, 3×) produced a decrease in rectal temperature of the animals after the first injection and an increase in the rectal temperature, peaking 30 min after the second and third injections. The arrows indicate the time of drug injection. Data represent mean ± S.E.M., n = 6 animals/group

Mentions: METH treatment (4 mg/kg, i.p., three injections given at 3 h intervals) resulted in significant changes in rectal temperatures (Fig. 1). The first injection of METH induced a marked hypothermic response (1.2°C below that of saline-treated mice), peaking at 30 min and lasting at least 1 h. The second and third injections caused transient hyperthermia (1–1.5°C above saline) which reached a peak 30 min after each injection. The highest value was reached after the second injection of METH reaching 39.2°C. Statistical comparison revealed a significant difference between the response of mice to METH and to saline within the first 60 min following the first, second, and third injections (P < 0.001 as by one-way ANOVA RM) (Fig. 1).Fig. 1


Selective vulnerability in striosomes and in the nigrostriatal dopaminergic pathway after methamphetamine administration : early loss of TH in striosomes after methamphetamine.

Granado N, Ares-Santos S, O'Shea E, Vicario-Abejón C, Colado MI, Moratalla R - Neurotox Res (2009)

Effect of METH on mouse rectal temperature. Repeated METH administration (4 mg/kg, i.p., every 3 h, 3×) produced a decrease in rectal temperature of the animals after the first injection and an increase in the rectal temperature, peaking 30 min after the second and third injections. The arrows indicate the time of drug injection. Data represent mean ± S.E.M., n = 6 animals/group
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2875475&req=5

Fig1: Effect of METH on mouse rectal temperature. Repeated METH administration (4 mg/kg, i.p., every 3 h, 3×) produced a decrease in rectal temperature of the animals after the first injection and an increase in the rectal temperature, peaking 30 min after the second and third injections. The arrows indicate the time of drug injection. Data represent mean ± S.E.M., n = 6 animals/group
Mentions: METH treatment (4 mg/kg, i.p., three injections given at 3 h intervals) resulted in significant changes in rectal temperatures (Fig. 1). The first injection of METH induced a marked hypothermic response (1.2°C below that of saline-treated mice), peaking at 30 min and lasting at least 1 h. The second and third injections caused transient hyperthermia (1–1.5°C above saline) which reached a peak 30 min after each injection. The highest value was reached after the second injection of METH reaching 39.2°C. Statistical comparison revealed a significant difference between the response of mice to METH and to saline within the first 60 min following the first, second, and third injections (P < 0.001 as by one-way ANOVA RM) (Fig. 1).Fig. 1

Bottom Line: In addition, the drug caused a reduction in TH- and DAT-immunoreactivity when compared to saline-treated animals.Interestingly, there was a significantly greater loss of TH- and DAT-immunoreactivity in striosomes than in the matrix.In contrast, METH did not decrease TH- or DAT-immunoreactivity in the nucleus accumbens.

View Article: PubMed Central - PubMed

Affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avda. Dr. Arce 37, 28002, Madrid, Spain.

ABSTRACT
Methamphetamine (METH), a commonly abused psychostimulant, causes dopamine neurotoxicity in humans, rodents, and nonhuman primates. This study examined the selective neuroanatomical pattern of dopaminergic neurotoxicity induced by METH in the mouse striatum. We examined the effect of METH on tyrosine hydroxylase (TH) and dopamine transporter (DAT) immunoreactivity in the different compartments of the striatum and in the nucleus accumbens. The levels of dopamine and its metabolites, 3,4-dihidroxyphenylacetic acid and homovanillic acid, as well as serotonin (5-HT) and its metabolite, 5-hydroxyindolacetic acid, were also quantified in the striatum. Mice were given three injections of METH (4 mg/kg, i.p.) at 3 h intervals and sacrificed 7 days later. This repeated METH injection induced a hyperthermic response and a decrease in striatal concentrations of dopamine and its metabolites without affecting 5-HT concentrations. In addition, the drug caused a reduction in TH- and DAT-immunoreactivity when compared to saline-treated animals. Interestingly, there was a significantly greater loss of TH- and DAT-immunoreactivity in striosomes than in the matrix. The predominant loss of dopaminergic terminals in the striosomes occurred along the rostrocaudal axis of the striatum. In contrast, METH did not decrease TH- or DAT-immunoreactivity in the nucleus accumbens. These results provide the first evidence that compartments of the mouse striatum, striosomes and matrix, and mesolimbic and nigrostriatal pathways have different vulnerability to METH. This pattern is similar to that observed with other neurotoxins such as MPTP, the most widely used model of Parkinson's disease, in early Huntington's disease and hypoxic/ischemic injury, suggesting that these conditions might share mechanisms of neurotoxicity.

Show MeSH
Related in: MedlinePlus