The effect of neurotoxic doses of methamphetamine on methamphetamine-conditioned place preference in rats

B. J. Gehrke, S. B. Harrod, W. A. Cass, M. T. Bardo

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Rationale: Methamphetamine has been shown to produce neurotoxicity demonstrated by depletions of dopamine and serotonin in the striatum and nucleus accumbens. Objective: The current study examined the effects of neurotoxic doses of methamphetamine on the rewarding effect of subsequent administration of methamphetamine assessed by the conditioned place preference (CPP) procedure. Methods: Male and female rats were treated with a neurotoxic regimen of methamphetamine (4x10 mg/kg, s.c., once every 2 h) or saline, and concentrations of dopamine, 3,4-dihydroxyphenylacetic acid, serotonin, and 5-hydroxyindoleacetic acid were measured 15 days later in the striatum, nucleus accumbens, and prefrontal cortex (PFC). In another experiment, male rats were given methamphetamine neurotoxic treatment or saline and were then conditioned 7 days later with methamphetamine (0.1, 0.3, or 1.0 mg/kg, s.c.) or saline using a four-trial CPP procedure. Locomotor activity was also measured during the conditioning sessions to investigate whether or not the neurotoxic methamphetamine treatment altered locomotor activity following a subsequent methamphetamine challenge. Results: Males and females did not differ significantly in the amount of neurochemical depletion produced by methamphetamine in any brain region. Collapsed across sex, dopamine was significantly depleted in nucleus accumbens (25%) and striatum (51%); serotonin was significantly depleted in nucleus accumbens (35%), striatum (34%) and PFC (33%). The methamphetamine challenge dose dependently increased locomotor activity, but the increase was not affected by treatment with neurotoxic doses of methamphetamine. In contrast, treatment with neurotoxic doses of methamphetamine enhanced CPP at the intermediate conditioning dose (0.3 mg/kg). Conclusions: These results indicate that the rewarding effect of methamphetamine is enhanced by prior treatment with neurotoxic doses of methamphetamine, suggesting either a compensatory hyperfunctioning of spared dopamine neurons or a loss of inhibitory control from serotonergic input.

Original languageEnglish
Pages (from-to)249-257
Number of pages9
Issue number3
StatePublished - Mar 2003

Bibliographical note

Funding Information:
Acknowledgements The authors would like to acknowledge the technical expertise of Natalie Johnson and Brenna Shortridge and the assistance of Jason Butler, Nathan Gilbertson, Uma Periya-nayagam, Allison Rathmann, Joey Regenbogen, and Keith Shar-row. Additionally, discussions with Susan Barron were helpful for the completion of this project. Research was supported in part by USPHS grant DA13519.


  • Conditioned place preference
  • Drug reward
  • Locomotor activity
  • Methamphetamine neurotoxicity
  • Sex differences

ASJC Scopus subject areas

  • Pharmacology


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