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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

The NAc does not exhibit METH-induced neurotoxicity. Photomicrographs of TH-immunoreactivity in the NAc of mice treated with saline (a) or METH (b). Animals were killed 7 days after treatment. c Histograms of the proportional stained area of TH-immunoreactivity. METH (4 mg/kg, i.p., every 3 h, 3×) produced no reduction in TH-immunoreactivity. Data represent mean ± S.E.M., P = 0.12; n = 6 animals/group. Bar 500 μm
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Fig7: The NAc does not exhibit METH-induced neurotoxicity. Photomicrographs of TH-immunoreactivity in the NAc of mice treated with saline (a) or METH (b). Animals were killed 7 days after treatment. c Histograms of the proportional stained area of TH-immunoreactivity. METH (4 mg/kg, i.p., every 3 h, 3×) produced no reduction in TH-immunoreactivity. Data represent mean ± S.E.M., P = 0.12; n = 6 animals/group. Bar 500 μm

Mentions: In contrast to our finding that administration of METH produces a marked loss of TH and DAT fibers in the striatum, we found no change in TH- or DAT-ir in the nucleus accumbens (NAc) (Fig. 7). Quantitative image analysis revealed no significant difference in TH-ir in the NAc between METH- and saline-treated mice 7 days after METH administration (P = 0.12) (Fig. 7c). These studies demonstrate that METH selectively reduces dopaminergic terminals in the striatum, but not in the NAc.Fig. 7


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)

The NAc does not exhibit METH-induced neurotoxicity. Photomicrographs of TH-immunoreactivity in the NAc of mice treated with saline (a) or METH (b). Animals were killed 7 days after treatment. c Histograms of the proportional stained area of TH-immunoreactivity. METH (4 mg/kg, i.p., every 3 h, 3×) produced no reduction in TH-immunoreactivity. Data represent mean ± S.E.M., P = 0.12; n = 6 animals/group. Bar 500 μm
© Copyright Policy
Related In: Results  -  Collection

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

Fig7: The NAc does not exhibit METH-induced neurotoxicity. Photomicrographs of TH-immunoreactivity in the NAc of mice treated with saline (a) or METH (b). Animals were killed 7 days after treatment. c Histograms of the proportional stained area of TH-immunoreactivity. METH (4 mg/kg, i.p., every 3 h, 3×) produced no reduction in TH-immunoreactivity. Data represent mean ± S.E.M., P = 0.12; n = 6 animals/group. Bar 500 μm
Mentions: In contrast to our finding that administration of METH produces a marked loss of TH and DAT fibers in the striatum, we found no change in TH- or DAT-ir in the nucleus accumbens (NAc) (Fig. 7). Quantitative image analysis revealed no significant difference in TH-ir in the NAc between METH- and saline-treated mice 7 days after METH administration (P = 0.12) (Fig. 7c). These studies demonstrate that METH selectively reduces dopaminergic terminals in the striatum, but not in the NAc.Fig. 7

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