Methamphetamine induces long-term changes in GABAA receptor alpha2 subunit and GAD67 expression.

Journal Article (Journal Article)

The present study investigated whether GABA(A) receptor alpha2 subunit and GAD(67) are involved in chronic high dose methamphetamine (METH)-induced sensitization and neurotoxicity. The METH sensitization was established in rats by 7-day pump infusion plus daily injection (25mg/kg/day) and a subsequent 28-day withdrawal period. Behavioral sensitization was assessed by behavioral ratings after challenge with METH (0.5mg/kg). The neurotoxicity was evaluated by the expression of glial fibrillary acidic protein (GFAP). Western blot assay showed that METH sensitization decreases GABA(A) alpha2 subunit and GAD(67) protein levels in the nucleus accumbens (NAc) core and shell, and conversely, these proteins were increased in the caudate. An upregulation of GFAP expression was observed in the caudate, but not in the NAc core and shell. These data suggest that inhibition of GABA transmission in the NAc is related to METH behavioral sensitization, whereas activation of GABA transmission in the caudate is associated with METH-induced neurotoxicity.

Full Text

Duke Authors

Cited Authors

  • Zhang, X; Lee, TH; Xiong, X; Chen, Q; Davidson, C; Wetsel, WC; Ellinwood, EH

Published Date

  • December 8, 2006

Published In

Volume / Issue

  • 351 / 1

Start / End Page

  • 300 - 305

PubMed ID

  • 17056007

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2006.10.046


  • eng

Conference Location

  • United States