Calcitriol protects against the dopamine- and serotonin-depleting effects of neurotoxic doses of methamphetamine

Wayne A. Cass, Michael P. Smith, Laura E. Peters

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

111 Scopus citations

Abstract

Repeated methamphetamine (METH) administration to animals can result in long-lasting decreases in brain dopamine (DA) and serotonin (5-HT) content. Calcitriol, the active metabolite of vitamin D, has potent effects on brain cells, both in vitro and in vivo, including the ability to upregulate trophic factors and protect against various lesions. The present experiments were designed to examine the ability of calcitriol to protect against METH-induced reductions in striatal and nucleus accumbens levels of DA and 5-HT. Male Fischer-344 rats were administered vehicle or calcitriol (1μg/kg, s.c.) once a day for eight consecutive days. After the seventh day of treatment the animals were given METH (5 mg/kg, s.c.) or saline four times in 1 day at 2-h intervals. Seven days later the striata and accumbens were harvested from the animals for high-performance liquid chromatography (HPLC) analysis of monoamines and metabolites. In animals treated with vehicle and METH, there were significant reductions in DA, 5-HT, and their metabolites in both the striatum and accumbens. In animals treated with calcitriol and METH, the magnitude of the METH-induced reductions in DA, 5-HT, and metabolites was substantially and significantly attenuated. The calcitriol treatments did not reduce the hyperthermia associated with multiple injections of METH, indicating that the neuroprotective effects of calcitriol are not due to the prevention of increases in body temperature. These results suggest that calcitriol can provide significant protection against the DA- and 5-HT-depleting effects of neuroioxic doses of METH.

Original languageEnglish
Title of host publicationCellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity
Subtitle of host publicationCocaine, GHB, and Substituted Amphetamines
Pages261-271
Number of pages11
DOIs
StatePublished - Aug 2006

Publication series

NameAnnals of the New York Academy of Sciences
Volume1074
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Accumbens
  • Calcitriol
  • Dopamine
  • Methamphetamine
  • Neurotoxicity
  • Serotonin
  • Striatum
  • Vitamin D

ASJC Scopus subject areas

  • Neuroscience (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • History and Philosophy of Science

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