Augmented methamphetamine-induced overflow of striatal dopamine 1 day after GDNF administration

Wayne A. Cass, Doriann J. Walker, Michael W. Manning

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Glial cell line-derived neurotrophic factor (GDNF) can attenuate the dopamine (DA)-depleting effects of neurotoxic doses of methamphetamine (METH) when given 1 day prior to the METH. The neurotoxic effects of METH may be due, in part, to sustained increases in extracellular levels of DA. It is therefore possible that GDNF may be altering the effects of METH by influencing extracellular levels of DA during the METH treatment. The purpose of the present study was to determine if GDNF has effects on extracellular levels of DA in the striatum by 24-h post-administration. GDNF (10 μg in 2 μ1 vehicle) or vehicle was injected into the right stratum or substantia nigra of anesthetized male rats. The next day the animals were anesthetized again and dialysis probes were positioned in both the right and left striata and perfused with artificial cerebrospinal fluid. Following the collection of baseline samples the rats were administered METH (5 mg/kg, s.c.). The METH injections dramatically increased extracellular DA levels on both sides of the brain. However, levels on the GDNF injected side were significantly greater than levels on the contralateral side. Basal levels of DA were not significantly different between the two sides, but levels of DA metabolites were elevated on the GDNF side. Post-mortem tissue levels of DA metabolites, but not DA, were also elevated in the striatum and substantia nigra. These results indicate that GDNF has significant effects on DA neuron functioning within 24 h of administration and that GDNF can augment DA overflow while inhibiting the neurotoxic effects of METH.

Original languageEnglish
Pages (from-to)104-112
Number of pages9
JournalBrain Research
Volume827
Issue number1-2
DOIs
StatePublished - May 8 1999

Bibliographical note

Funding Information:
This work was supported in part by USPHS grant DA 10115. We thank Ms. LuAnne Perry for technical assistance and Synergen (Boulder, CO) and Amgen (Thousand Oaks, CA) for the generous gift of GDNF.

Keywords

  • Dopamine
  • GDNF
  • In vivo microdialysis
  • Methamphetamine
  • Neurotrophic factor
  • Striatum
  • Substantia nigra

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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