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Recovery of presynaptic dopaminergic functioning in rats treated with neurotoxic doses of methamphetamine.

Publication ,  Journal Article
Cass, WA; Manning, MW
Published in: J Neurosci
September 1, 1999

Repeated administration of methamphetamine (METH) to animals can result in long-lasting decreases in striatal dopamine (DA) content. In addition, the evoked overflow of striatal DA is reduced in rats 1 week after neurotoxic doses of METH. However, whether these functional changes in DA release are permanent or tend to recover over time has not been established. In the present study we used in vivo electrochemistry and microdialysis to examine evoked overflow of DA in the striatum of METH-treated rats at several time points after treatment to determine if DA overflow would spontaneously recover. Male Fischer-344 rats were administered METH (5 mg/kg, s.c. ) or saline four times in one day at 2 hr intervals. In vivo electrochemistry experiments in anesthetized rats, and in vivo microdialysis studies in awake rats, were carried out 1 week, 1 month, 6 months, and 12 months after treatment. At 1 week after treatment there were significant decreases in potassium- and amphetamine-evoked overflow of DA, and in clearance of DA, in the striatum of the METH-treated animals. Basal extracellular levels of DA and its metabolites were also decreased. Evoked overflow had partially recovered by 1 month. By 6 months evoked overflow of DA appeared to be normal in the METH-treated rats. However, whole tissue levels of striatal DA were still significantly decreased. All parameters were back to control values by 12 months. These results suggest that presynaptic dopaminergic functioning can recover to normal levels in the striatum of METH-treated rats by 12 months after treatment.

Duke Scholars

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

September 1, 1999

Volume

19

Issue

17

Start / End Page

7653 / 7660

Location

United States

Related Subject Headings

  • Wakefulness
  • Time Factors
  • Rats, Inbred F344
  • Rats
  • Presynaptic Terminals
  • Potassium
  • Nucleus Accumbens
  • Neurotoxins
  • Neurology & Neurosurgery
  • Microdialysis
 

Citation

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Cass, W. A., & Manning, M. W. (1999). Recovery of presynaptic dopaminergic functioning in rats treated with neurotoxic doses of methamphetamine. J Neurosci, 19(17), 7653–7660. https://doi.org/10.1523/JNEUROSCI.19-17-07653.1999
Cass, W. A., and M. W. Manning. “Recovery of presynaptic dopaminergic functioning in rats treated with neurotoxic doses of methamphetamine.J Neurosci 19, no. 17 (September 1, 1999): 7653–60. https://doi.org/10.1523/JNEUROSCI.19-17-07653.1999.
Cass, W. A., and M. W. Manning. “Recovery of presynaptic dopaminergic functioning in rats treated with neurotoxic doses of methamphetamine.J Neurosci, vol. 19, no. 17, Sept. 1999, pp. 7653–60. Pubmed, doi:10.1523/JNEUROSCI.19-17-07653.1999.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

September 1, 1999

Volume

19

Issue

17

Start / End Page

7653 / 7660

Location

United States

Related Subject Headings

  • Wakefulness
  • Time Factors
  • Rats, Inbred F344
  • Rats
  • Presynaptic Terminals
  • Potassium
  • Nucleus Accumbens
  • Neurotoxins
  • Neurology & Neurosurgery
  • Microdialysis