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Methamphetamine Induces Low Levels of Neurogenesis in Striatal Neuron Subpopulations and Differential Motor Performance

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Abstract

Methamphetamine (METH) causes significant loss of some striatal projection and interneurons. Recently, our group reported on the proliferation of new cells 36 h after METH and some of the new cells survive up to 12 weeks (Tulloch et al., Neuroscience 193:162–169, 2011b). We hypothesized that some of these cells will differentiate and express striatal neuronal phenotypes. To test this hypothesis, mice were injected with METH (30 mg/kg) followed by a single BrdU injection (100 mg/kg) 36 h after METH. One week after METH, a population of BrdU-positive cells expressed the neuronal progenitor markers nestin (18 %) and β-III-tubulin (30 %). At 8 weeks, 14 % of the BrdU-positive cells were also positive for the mature neuron marker, NeuN. At 12 weeks, approximately 7 % of the BrdU-positive cells co-labeled with ChAT, PV or DARPP-32. We measured motor coordination on the rotarod and psychomotor activity in the open-field. At 12 weeks, METH–injected mice exhibited delayed motor coordination deficits. In contrast, open-field tests revealed that METH-injected mice compared to saline mice displayed psychomotor deficits at 2.5 days but not at 2 or more weeks after METH. Taken together, these data demonstrate that some of the new cells generated in the striatum differentiate and express the phenotypes of striatal neurons. However, the proportion of these new neurons is low compared to the proportion that died by apoptosis 24 h after the METH injection. More studies are needed to determine if the new neurons are functional.

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Abbreviations

BrdU:

5-Bromo-2′-deoxyuridine

ICR:

Institute for Cancer Research

Ip:

Intraperitoneal

METH:

(+)-Methamphetamine hydrochloride

PBS:

Phosphate-buffered saline, pH 7.4

IB4:

Isolectin B4

NeuN:

Neuron nuclear protein

ChAT:

Choline acetyltransferase

DA:

Dopamine

DARPP-32:

Dopamine and cAMP-regulated phosphoprotein of 32 kDa

PV:

Parvalbumin

SVZ:

Sub-ventricular zone

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Acknowledgments

This study was supported by R01 DA020142 from the National Institute on Drug Abuse to JAA. Support for infrastructure came from a grant from the National Center for Research Resources (G12 RR003037) and the National Institute on Minority Health Disparities (8 G12 MD007599) awarded to Hunter College by the NIH. We would like to thank Drs. Cheryl Harding and Peter Serrano for use of their behavior testing equipment.

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Authors and Affiliations

  1. Department of Biological Sciences, Hunter College, 695 Park Avenue, New York, NY, 10065, USA

    I. K. Tulloch, L. Afanador, L. Baker, D. Ordonez, H. Payne, I. Mexhitaj, E. Olivares, A. Chowdhury & J. A. Angulo

  2. The Graduate Center of The City University of New York, New York, NY, USA

    I. K. Tulloch, L. Afanador & J. A. Angulo

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  1. I. K. Tulloch
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  2. L. Afanador
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  3. L. Baker
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  4. D. Ordonez
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  5. H. Payne
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  6. I. Mexhitaj
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  7. E. Olivares
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  9. J. A. Angulo
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Correspondence to J. A. Angulo.

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Tulloch, I.K., Afanador, L., Baker, L. et al. Methamphetamine Induces Low Levels of Neurogenesis in Striatal Neuron Subpopulations and Differential Motor Performance. Neurotox Res 26, 115–129 (2014). https://doi.org/10.1007/s12640-014-9456-1

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